The Timing of Clinical Effects of Bupropion Misuse Via Insufflation Reported to a Regional Poison Center.

BACKGROUND: Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window that can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via insufflation, which added a layer of complexity with regards to the therapeutic application of the drug. This route of use created difficult decisions regarding clinical monitoring in these patients. OBJECTIVES: To determine if prolonged observation is required after insufflation of bupropion and to further describe effects from this route of use. METHODS: This is a retrospective observational study reviewing all the cases of insufflated bupropion use reported to a single poison center without any other coingestants. RESULTS: The majority (85.7%) of patients had mild or moderate effects, and seizures occurred in 19.6% of cases; and the vast majority of patients were symptomatic by the time of the initial call to the poison center. We did not encounter any delayed effects after this route of use. CONCLUSIONS: This report describes the clinical effects reported, and the timing of these effects, after insufflation of bupropion.

Clinical effects of intravenous bupropion misuse reported to a regional poison center.

Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window which can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via intravenous use and had difficulty guiding decisions regarding clinical monitoring in these patients. As this route entirely changes the kinetics of bupropion, this has caused concern within our group. We reviewed all the cases of intravenous bupropion use reported to a single poison center without any other coingestants. The majority (66.7%) of patients had moderate effects and one patient had a seizure. No deaths were reported. All patients were symptomatic by the time of initial call to the poison center if they had any reported symptoms due to bupropion. This case series describes the clinical effects reported, and the timing of these effects, after intravenous bupropion use.

Point-of-sale Naloxone: Novel Community-based Research to Identify Naloxone Availability.

INTRODUCTION: Expanding naloxone availability is important to reduce opioid-related deaths. Recent data suggest low, variable urban naloxone availability. No reports describe naloxone availability at the point of sale (POSN). We characterize POSN without prescription across a Midwestern metropolitan area, via a unique poison center-based study. METHODS: Pharmacies were randomly sampled within a seven-county metropolitan area, geospatially mapped, and distributed among seven investigators, who visited pharmacies and asked, "May I purchase naloxone here without a prescription from my doctor?" Following "No," investigators asked, "Are you aware of the state statute that allows you to dispense naloxone to the public under a standing order?" Materials describing statutory support for POSN were provided. Responses were uploaded to REDCap in real time. We excluded specialty (veterinary, mail order, or infusion) pharmacies a priori. POSN availability is presented as descriptive statistics; characteristics of individual sites associated with POSN availability are reported. RESULTS: In total, 150 pharmacies were prospectively randomized, with 52 subsequently excluded or unavailable for survey. Thus, 98 were included in the final analysis. POSN was available at 71 (72.5%) of 98 pharmacies. POSN availability was more likely at chain than independent pharmacies (84.7% vs 38.5%, p<0.001); rural areas were more commonly served by independent than chain pharmacies (47.4% vs 21.5%, p = 0.022). Five chain and five independent pharmacies (18.5% each) were unaware of state statutory support for collaborative POSN agreements. Statutory awareness was similar between independent and chain pharmacies (68.8% vs 54.6%, p = 0.453). Rationale for no POSN varied. CONCLUSION: POSN is widely available in this metropolitan area. Variability exists between chain and independent pharmacies, and among pharmacies of the same chain; awareness of statutory guidance does not. Poison centers can act to define local POSN availability via direct inquiry in their communities.

Death Associated With Nadolol for Infantile Hemangioma: A Case for Improving Safety.

Nadolol is a ß-adrenergic antagonist that has been shown to be efficacious in the treatment of infantile hemangioma. It has been suggested that this drug may have fewer side effects compared with the gold standard therapy, propranolol, because it does not exhibit membrane-stabilizing effects and has little ability to cross the blood-brain barrier. However, the pharmacokinetics and safety of nadolol in infants are not well understood, potentially making this therapy dangerous. ß-adrenergic antagonist toxicity causes bradycardia, hypotension, hypoglycemia, and even death. We report a case of a 10-week-old girl who was started on nadolol for infantile hemangioma, died 7 weeks later, and was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. The infant had no bowel movements for 10 days before her death, which we hypothesize contributed to nadolol toxicity. Pharmacokinetics studies show a large fraction of oral nadolol either remains in the feces unchanged or is excreted into feces via the biliary system, allowing continued absorption over time in infants who stool infrequently. Propranolol may be a safer therapy overall. Not only does it have a shorter half-life, but propranolol is hepatically metabolized and renally eliminated, allowing for less drug accumulation in healthy infants with variable stooling patterns. We suggest that if nadolol is selected for therapy, pediatricians should instruct parents to monitor their infants' bowel movements closely and encourage early intervention in the event of decreased stooling. This intervention may greatly improve the safety of nadolol in this vulnerable patient population.

Octreotide for the treatment of intentional insulin aspart overdose in a non-diabetic patient.

Intentional insulin overdose may lead to severe and refractory hypoglycemia. Exogenous dextrose administration is the mainstay of therapy for these patients and is effective in most cases. However, in patients with a functional pancreas, exogenous dextrose administration may precipitate endogenous insulin release leading to rebound hypoglycemia. We describe a case report of a 41-year-old woman who injected 300 units of insulin aspart with suicidal intent. Her initial blood glucose was 2.3 mmol/L (41 mg/dL). Over the next 12 hours, she experienced recurrent hypoglycemic episodes despite 10% dextrose infusions and 14 ampoules of 50% dextrose. Our patient experienced complications, including peripheral edema, related to the large volumes of intravenous dextrose required to attempt to maintain euglycemia. Octreotide, a somatostatin analogue, may help prevent dextrose-induced hypoglycemia and improve the management in select insulin overdose patients; large infusion volumes resulted in significant peripheral edema. Treatment with octreotide was initiated 12.5 hours post-injection and was followed by a stabilization of blood glucose concentration in this non-diabetic patient.

Therapeutic induced hypothermia does not improve the prognosis of out-of-hospital cardiac arrest patients.

Unconscious patients admitted to critical care units after out-of-hospital cardiac arrest are at high risk for death, and neurologic deficits are common among those who survive. The target temperature management (TTM), 33 vs. 36 °C, after out-of-hospital cardiac arrest trial was conducted to assess the benefits and harms of two targeted temperature regimens after out-of-hospital cardiac arrest of presumed cardiac cause. The study randomized 950 unconscious survivors of out-of-hospital cardiac arrest with presumed cardiac cause to a target temperature of 33 vs. 36 °C following return of spontaneous circulation (ROSC), irrespective of the initial rhythm. At the end of the trial, 50% of the patients in the 33 °C group (235 of 473 patients) had died, as compared to 48% of the patients in the 36 °C group (225 of 466 patients) [hazard ratio with a temperature of 33 °C 1.06; 95% confidence interval (CI) 0.89-1.28; p = 0.51]. In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 °C does not confer a survival benefit as compared to a targeted temperature of 36 °C.