Guanfacine toxic ingestion with subsequent cardiogenic pulmonary edema.

Guanfacine is a central alpha-2 agonist often prescribed for Attention-deficit hyperactive disorder as well as tic disorder, with a usual dose of 1-4 mg per day. Due to its sympatholytic mechanism of action, Guanfacine can cause autonomic instability and hypotension. It can additionally cause cardiac dysfunction to include symptomatic bradycardias and contractility suppression. The authors present a case of a 17 year-old male with an ingestion of 80 mg of extended release Guanfacine with delayed onset cardiogenic pulmonary edema requiring mechanical ventilation. Previous pediatric ingestions have generated bradycardia, hypotension, and decreased level of consciousness, responsive to intravenous fluids, vasopressors, and occasionally naloxone. However, cardiogenic pulmonary edema from reduced cardiac contractility is a novel consequence of extended release Guanfacine ingestion. With Guanfacine's extended half-life, this unique case underscores the importance of emergency providers' familiarity with this toxidrome as well the necessity for prolonged, close observation following Guanfacine ingestion.

Pediatric guanfacine exposures reported to the National Poison Data System, 2000-2016.

Introduction: The purpose of this study was to characterize the frequency, reasons for exposure, clinical manifestations, treatments, duration of effects, and medical outcomes of pediatric guanfacine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016.Methods: Data extracted from poison control center call records for pediatric (0-5 years, 6-12 years, and 13-19 years), single-substance guanfacine ingestions reported to NPDS between 2000 and 2016 was retrospectively analyzed.Results: A total of 10927 cases were identified for analysis. Pediatric single-substance guanfacine exposures reported to NPDS increased significantly during the study period, with a marked increase among 6-12-year-olds. The most commonly documented clinical effects across age groups were drowsiness (n = 4262, 39%), bradycardia (n = 1696, 15.5%), and hypotension (n = 1127, 10.3%). The duration of effect for most cases was >8 hours but ≤24 hours (n = 2395, 44.2%). The median documented quantity of guanfacine ingested was 0.11 mg/kg (range: 0.004-7.8 mg/kg). The difference between mg/kg ingested in no effect and minor effect groups compared to moderate and major effect groups was statistically significant in all three age groups.Conclusions: Pediatric guanfacine exposures reported to U.S. poison centers have increased significantly in the last fifteen years. The most common clinical findings secondary to guanfacine exposure were bradycardia, hypotension, and CNS depression. There was a statistically significant difference between the mg/kg of guanfacine ingested in the groups experiencing no effect or mild effect compared to moderate or major effects. However, the maximum ingested dose reported among 0-5-year-olds in the no effect group was 2.72 mg/kg, while the minimum dose eliciting a major effect in both 0-5 and 6-12-year-olds was 0.05 mg/kg. The overall incidence of major effects was very low, with the vast majority of patients experiencing minor symptoms or less. Based on this data, we agree with current recommendations that any symptomatic pediatric patient exposed to guanfacine should be observed in a health care facility for at least 24 hours.

Unintentional pediatric exposures to central alpha-2 agonists reported to the National Poison Data System.

OBJECTIVE: To investigate national trends in unintentional pediatric exposures to 3 common alpha-2 agonists: clonidine, guanfacine, and tizanidine. Secondary objectives were to describe outcomes, symptoms, treatments, and death. STUDY DESIGN: Retrospective chart review from the American Association of Poison Control Centers National Poison Data System from January 2000 to December 2011 for unintentional exposure to clonidine, guanfacine, and tizanidine in children ≤ 12 years of age. RESULTS: From 2000-2011, there was a significant increase (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National Poison Data System for central alpha-2 agonists. There were 27,825 clonidine exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8% male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age: 2 years). Guanfacine had the greatest proportional increase among the medications. Clonidine was associated with the most respiratory (799, 2.9%) and central nervous system symptoms (12,612, 45.3%), as well as the most episodes of bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty-eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine. CONCLUSIONS: The number of unintentional pediatric exposures to alpha-2 agonists increased from 2000-2011. Clonidine exposures were the most commonly reported, more symptomatic, and associated with 3 deaths. Despite central nervous system depression, bradycardia, and hypotension being common, the need for intubation and vasopressors was rare.

An overdose of extended-release guanfacine.

Extended-release guanfacine is a centrally acting α2-adrenergic agonist that was recently approved for treatment of attention-deficit/hyperactivity disorder. The following is a case discussion of a 12-year-old boy with attention-deficit/hyperactivity disorder and Tourette syndrome, who presented 18 hours after ingestion of 3 times his usual dose of extended-release guanfacine. On presentation, he was lethargic, bradycardic, and hypertensive with an otherwise nonfocal neurological examination. He remained hypertensive until administration of an intravenous antihypertensive agent (nicardipine) 24 hours after ingestion. After cessation of the calcium-channel blocker, he continued to have intermittent episodes of symptomatic hypotension for the next 2½ days. This extremely protracted course of hypertension followed by prolonged symptomatic hypotension is rare with ingestions of centrally acting α2-adrenergic agonists. As this drug is increasingly prescribed for treatment of a disease with increasing prevalence, it is imperative that emergency physicians become familiar with the varying presentations of its toxicity.

Guanfacine overdose resulting in initial hypertension and subsequent delayed, persistent orthostatic hypotension.

INTRODUCTION: Guanfacine is an alpha(2)-adrenoreceptor agonist used for the treatment of attention-deficit hyperactivity disorder and tic disorders. Few reports exist regarding overdose with guanfacine. CASE REPORT: A 16-year-old female with Tourette's syndrome presented with diaphoresis, dry mouth, and hypertension 8 h after ingesting 25 mg of guanfacine. These symptoms improved and her blood pressure (BP) normalized over 2 h. Thirty hours following ingestion, she experienced near syncope and returned to the emergency department. She was noted to have orthostatic hypotension and a prolonged QTc interval of 593 ms on electrocardiogram. With only fluid support, she was asymptomatic by 60 h postingestion and her QTc interval had improved to 511 ms. DISCUSSION: This experience suggests a much delayed onset of symptoms may occur and that the QTc interval may be prolonged, necessitating a longer period of monitoring in a patient presenting with an overdose.