Marcel J. Casavant

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, 696 937 children <6 years experienced out-of-hospital medication errors, averaging 63 358 episodes per year, or 1 child every 8 minutes. The average annual rate of medication errors was 26.42 per 10 000 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 17 230 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.

Urine drug screening in adolescents.

The urine drug screen is an important tool in adolescent medicine. Several ethical, and numerous technical, issues are associated with the use of this tool. The nature and limitations of the specific tests of which the screen is composed must be known to the physician. Two-way communication with the laboratory, both before the test is ordered and after the results are reported, can be very helpful. Laboratory testing cannot substitute for an ongoing therapeutic alliance with the patient. Testing is an important element of the substance use assessment, but is only one element, is not required in every case, and is not sufficient alone in any case.

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 29 141 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 12.5 ng/ml, (range 0.5 ng/ml to >40 ng/ml). Mean norfentanyl concentrations were 1.9 ng/ml (range none detected to 8.3 ng/ml). No appreciable concentrations of norfentanyl could be detected in 20 of 48 cases (42%) and were less than 1 ng/ml in 25 cases (52%). Elevated fentanyl concentrations did not correlate with rises in norfentanyl levels. In several cases fentanyl concentrations were strikingly high (22 ng/ml and 20 ng/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 (1–2 ng/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.

Atomoxetine-induced hepatitis in a child

Objective. To report a case of hepatitis associated with atomoxetine hydrochloride use and to describe the previously-unpublished severe cases of this syndrome. Case summary. An eight-year-old female with attention deficient hyperactive disorder (ADHD) was treated with atomoxetine hydrochloride. She complained of increased abdominal pain and occasional emesis; her transaminases and bilirubin were markedly elevated. She was admitted to a tertiary-care pediatric hospital and treated for drug-induced hepatitis. Atomoxetine was discontinued and supportive care was instituted. A liver biopsy showed hepatitis with moderate piecemeal necrosis. Clinical status and liver function tests improved over 13 days of hospitalization. Discussion. To our knowledge this is the first published severe case of atomoxetine-induced hepatitis. The International Organization of Medical Science Diagnostic Scale and the Adverse Drug Reaction Probability Scale by Naranjo et al. were applied to assess causality. Both scales indicated the association of atomoxetine and hepatitis as “probable;” a positive rechallenge would have made this association “definitive.” This potential serious adverse reaction should be considered in children receiving atomoxetine therapy.

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

From 2000 through 2015, 188 468 pediatric prescription opioid exposures were reported to US poison control centers. The rate of opioid-related suspected suicides among teenagers increased by >50%. OBJECTIVES: This study analyzes and compares exposures to prescription opioids among children and adolescents younger than 20 years old in the United States. METHODS: Data from the National Poison Data System for 2000 through 2015 were analyzed. RESULTS: Poison control centers received reports of 188 468 prescription opioid exposures among children aged <20 years old from 2000 through 2015. The annual number and rate of exposures increased early in the study period, but declined after 2009, except for buprenorphine exposures, which increased during the last 3 study years. Hydrocodone accounted for the largest proportion of exposures (28.7%), and 47.1% of children exposed to buprenorphine were admitted to a health care facility (HCF). The odds of being admitted to an HCF were higher for teenagers than for children aged 0 to 5 years (odds ratio [OR]: 2.86; 95% confidence interval [CI]: 2.78–2.94) or children aged 6 to 12 years (OR: 6.62; 95% CI: 6.06–7.02). Teenagers also had greater odds of serious medical outcomes than did children aged 0 to 5 years (OR: 3.03; 95% CI: 2.92–3.15) or children aged 6 to 12 years (OR: 4.59; 95% CI: 4.21–5.00). The rate of prescription opioid–related suspected suicides among teenagers increased by 52.7% during the study period. CONCLUSIONS: Prescription opioid–related HCF admissions and serious medical outcomes were higher among teenagers. Contrary to trends for other prescription opioids, exposures to buprenorphine have increased in recent years; children aged 0 to 5 years accounted for almost 90% of buprenorphine exposures. These findings indicate that additional prevention efforts are needed.

Marijuana Exposure Among Children Younger Than Six Years in the United States

This study investigates marijuana exposures among children <6 years old in the United States using data from the National Poison Data System. From 2000 through 2013, there were 1969 marijuana exposures among children <6 years old and an exposure rate of 5.90 per million children. The mean age of an exposed child was 1.81 years (median = 1.58 years). The majority of the children were exposed through ingestion (75.0%), and 18.5% of exposures required admission to a health care facility. The rate of marijuana exposure was significantly (2.82 times) higher in states where its use was legalized prior to 2000 compared with states where its use is not legal. Because more states are likely to pass legislation legalizing medical and recreational use of marijuana, increased efforts to establish child-focused safety requirements regarding packaging of commercially sold marijuana products are needed to help prevent more children from being exposed to this schedule I substance.

Plasma salicylate from methyl salicylate cream compared to oil of wintergreen.

Background. Poison Control Centers follow the acetylsalicylic acid (ASA) treatment guideline to manage unintentional ingestions of topical methyl salicylate liniments. For example, one teaspoon of 30% methyl salicylate cream such as Ben Gay® provides an “ASA equivalent dose” of 180 mg/kg for a 10 kg child. The ASA treatment guideline advises emesis with syrup of Ipecac and 24 h home followup for this dose. Both the ASA conversion factor to yield the ASA equivalent dose and the treatment guideline assume 100% bioavailability of the salicylate. The nature of this topical dosage product led the investigators to expect less than complete absorption of methyl salicylate. Objective. To compare plasma concentrations of salicylate from ingested methyl salicylate cream with plasma concentrations of salicylate from ingested oil of wintergreen. Methods. Four adult volunteers consented to an open label, four-way crossover design, with randomization to the following treatments: 1 mL Oil of Wintergreen, U.S.P., 6.7 g of Ben Gay® 15% and 20 g of Ben Gay® 15% and also to hold 5 g of Ben Gay® 15% cream in the buccal cavity for 1 minute and then expectorate. Plasma was collected for salicylate determination, and the results analyzed with a noncompartmental pharmacokinetic model. Results. No plasma salicylate was detected after buccal treatment phase. Relative bioavailability for the low-dose treatment was 0.5 compared to oil of wintergreen. Conclusion. Plasma salicylate concentrations from methyl salicylate cream are not equal to those achieved after ingestion of oil of wintergreen. Dosage formulation must be considered when predicting toxicity.

Children and Adolescent Exposures to Atomoxetine Hydrochloride Reported to a Poison Control Center

Background. Atomoxetine hydrochloride, a selective norepinephrine reuptake inhibitor was FDA approved for patients with attention-deficit/hyperactivity disorder. Little is known about adverse drug reactions of atomoxetine following an overdose among children. The objective of our study was to evaluate the type of atomoxetine adverse drug reactions in relation to dose. Methods. We evaluated children exposed to atomoxetine reported to a poison center from January-December 2004. Results. Sixty-four cases met all inclusion criteria. Twenty-one patients had an adverse drug reaction (15 at dosage range 0.52–6.25 mg/kg): agitation, headache, erythema, rash, elevated blood pressure and heart rate, nausea, emesis, and lethargy. In 51 patients, weights were known: group 1 (n = 43) received higher than maximum recommended doses >1.4 mg/kg and group 2 (n = 8) received ≤1.4 mg/kg. There were no differences in adverse drug reactions in group 1 versus 2. Eight patients were admitted to a healthcare facility and all were discharged without any sequelae. Hypertension occurred in 3 of 9 patients for whom blood pressure was recorded. Conclusion. At the doses reported, adverse drug reactions did not correlate with atomoxetine dose. Hypertension may occur in some patients following atomoxetine overdose.