Characterizing the Toxicity and Dose-Effect Profile of Tramadol Ingestions in Children.

OBJECTIVES: Tramadol can cause life-threatening toxicity in overdose; however, data on its toxicity in children are lacking. This study investigates toxicity associated with tramadol ingestions in children. The hypothesis is that children will experience dose-related central nervous system and respiratory depression and seizures. METHODS: A retrospective evaluation of cases from the National Poison Center Data System between January 1, 2000, and December 31, 2013, was performed. Inclusion criteria were age below 6 years and single-substance acute tramadol ingestion. For dose-effect analysis, cases with sufficient dose quantity information were included. RESULTS: There were 7334 cases that met inclusion criteria. Outcomes were 84.8% no effect, 12.6% minor, 2.2% moderate, and 0.4% major effect. There was 1 fatality. Most of the children (36.4%) were treated/released from the emergency department; other management sites were home (36.4%), admission (5.9%), and others (3.2%). In the 1115 children with symptoms, drowsiness (N = 611) and vomiting (N = 178) occurred most frequently. More serious clinical effects included respiratory depression in 36 and seizures in 24 children. Of 2772 children with milligram dose recorded, there were 10 cases of respiratory depression and 6 of seizure. Median doses for respiratory depression and seizure were 225 (range, 50-600 mg) and 525 mg (range, 50-1050 mg), respectively. The minimum weight-based dose for respiratory depression/arrest was 7.9 mg/kg and for seizures, 4.8 mg/kg. CONCLUSIONS: Seizure and respiratory depression are uncommon in pediatric tramadol ingestions. Given the small number of patients with dose data and lack of laboratory confirmation of dose, more studies are needed to determine the minimum dose at which medical management is recommended.

Bupropion "Abuse" Reported to US Poison Centers.

OBJECTIVES: Bupropion use to obtain nonmedical psychoactive effects has been reported. The objective was to determine the prevalence, characteristics, clinical effects, and outcomes of bupropion "abuse." METHODS: A 14-year retrospective review was conducted of single substance bupropion cases with "intentional abuse" as the coded reason for exposure in individuals 13 and older reported to the National Poison Data System. Data were evaluated for prevalence, demographics, clinical effect, route, final management site, and coded outcome. RESULTS: There were 975 bupropion abuse cases, which accounted for 3.3% of single substance bupropion cases reported to US poison centers. The prevalence of abuse increased by 75%, from 2000 to 2012, declining slightly in 2013. The majority of cases were 13 to 29 years old (67.4%). The most frequent clinical effects were tachycardia (57.0%), seizures (33.5%), agitation/irritable (20.2%), hallucinations/delusions (14.0%), and tremor (13.1%). Most exposures were ingestions (745) followed by insufflation (166), parenteral (17), and other/unknown (17); 30 cases involved 2 routes. Seizure frequency was not significantly different between routes (P = 0.783) or exposure chronicity (P = 0.264). Final management sites were predominantly emergency department (36.9%) and admission to critical care unit (27.3%) or noncritical care unit (20.1%). Outcomes were major (11.4%), moderate (48.2%), minor (24.5%), and no effect (15.5%). There were 4 deaths. CONCLUSIONS: Most bupropion abuse occurs in adolescents and young adults. Tachycardia and seizures are common indicating the potential for serious effects. Seizures occur regardless of route. Providers should be aware of risk of bupropion abuse.

Treatment of sulfonylurea and insulin overdose.

The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l(-1) . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide.