Faculty Bibliography

The use of medicines, with or without medical prescription, for recreational ends by the young population has received little attention from doctors. In the USA, one in five adolescents has used medicines for recreational purposes, and consultations in Emergency Departments for medicine abuse have exceeded those for illegal drugs. Although few data are available in Spain, such consumption is situated between 3.1 and 8.6% according to surveys. The medicines most used are dextromethorphan and methylphenidate. The former, on sale without prescription, presents a varied symptomatology, dosage and dependent metabolic action, ranging from euphoria to hallucinations. Methylphenidate, taken orally, nasally or intravenously, is used as a stimulant in substitution for cocaine and is one of the medicines most diverted onto the illicit market at the world level. In principle, other substances like modafinil and propofol present a limited incidence of non-medical use, but they have a probable abuse potential that should be borne in mind, above all in the health context. Finally, opiates like fentanyl, oxycodone and buprenorphine, with new pharmaceutical presentations, have recently become generalized in the therapeutic arsenal of many medical specialities; they are giving rise to phenomena of abuse, dependence and diversion towards the illicit market. Demands for detoxification treatment, their mixture with illegal substances, and cases of death should alert us to the abuse of these medicines.

Background: We recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of emergency department (ED) patients with acute drug overdose. It remains unclear which patients require intensive care unit admission or telemetry monitoring to assess for in-hospital ACVE. Objectives: This study derived clinical risk factors for ACVE in ED patients with acute drug overdose. Methods: This prospective cohort study was conducted at two urban university tertiary care hospitals. Patients >18 years with acute drug overdose were enrolled from the ED over 3 years. Excluded were patients with alternate diagnoses, anaphylaxis, chronic drug toxicity, and missing outcome data. ED clinical data included demographics, exposure intent, ECG intervals, vital signs, laboratory chemistries, altered mental status (GCS <15 or coma/agitation/delirium), and prior cardiac disease (coronary disease or congestive heart failure). Inhospital ACVE was defined as any of: 1) myocardial necrosis (elevated troponin), 2) shock (hypotension requiring vasopressors), 3) ventricular tachycardia or fibrillation (VTVF), or 4) cardiac arrest (no pulses or chest compressions). Analysis included univariate factor analysis and multivariable logistic regression with test characteristics of the derived model. Results: There were 1,557 patients meeting inclusion/exclusion criteria with mean age 41.8 years, female 46%, suicidal 38%, median drug exposures = 2. ACVE occurred in 82 (5.7%) patients including: myocardial necrosis, 61; shock, 37; VTVF, 23; and 22 cardiac arrests with 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age (p<0.001), lower serum bicarbonate (p<0.001), prolonged QTc (p<0.001), prior cardiac disease (p<0.001), and altered mental status (p 0.05). In a multivariable model adjusting for these factors as well as sex and ED site, independent predictors included: 1) QTc > 500 msec, 2) bicarbonate <20 mEq/L, and 3) prior cardiac disease. Test characteristics of these ACVE risk factor!

Background: Drug overdose is the leading cause of injury-related mortality in the USA, but the prognostic utility of cardiac biomarkers is unknown. Objectives: We hypothesized that elevated serum cardiac troponin I (cTnI) would predict overdose mortality. Methods: Prospective observational cohort at two urban university hospital EDs enrolled consecutive adults > 18 years with suspected acute drug overdoses over 3 years (2009-12). Patients without cTnI or missing follow-up (transfer, leave against medical advice, etc) were excluded. Data included demographics, vital signs, prior coronary artery disease (CAD), urine cocaine metabolite, and cardiac biomarkers (CK, CKMB%, cTnI) drawn at the bedside for routine clinical care. The endpoint was in-hospital mortality, which was used to determine test characteristics of cTnI using ROC curves. Assuming 5% prevalence of elevated cTnI overall, we calculated the need to analyze 435 subjects to show a 5% difference (80% power, 5% alpha). Results: Out of 845 overdoses (mean age 38, 48% female), 438 (52%) had cTnI results available, with 20 (2.4%) deaths. Clinicians were more likely to order cTnI in patients with known prior CAD; however, there were no substantial differences in other clinical variables between groups. Abnormal vital signs (i.e. tachycardia, bradycardia, hypotension) were not substantially different in the groups with mortality or elevated cTnI. The table outlines the biomarker test characteristics to predict mortality. Mean initial cTnI was significantly higher in the mortality group (1.2 vs. 0.06 ng/mL, p<0.001). The ROC curve is displayed in the figure. Initial cTnI was normal in only one death out of the entire cohort (1/438 or 0.2%). Conclusion: Initial cTnI has excellent diagnostic test characteristics to predict acute drug overdose mortality. Future research should focus on high-risk overdose features to optimize strategies for utilization of cTnI as part of the workup for acute drug overdose. (Table Presented)

Dabigatran is an oral direct thrombin inhibitor indicated for thromboembolism prophylaxis in patients with nonvalvular atrial fibrillation. Since its approval in the United States in 2010, dabigatran-associated hemorrhages have garnered much attention because bleeding rates were higher than initially expected. Additionally, reversing anticoagulation remains challenging. Traditional modes of reversing warfarin-associated coagulopathies are ineffective in reversing anticoagulation from dabigatran. Although hemodialysis is proposed as a method to accelerate dabigatran elimination, evidence supporting its clinical utility remains unproved. We report the case of an 80-year-old man who presented with worsening hemoptysis in the setting of unintentional ingestion of excess dabigatran. Despite transfusion of 2 units of fresh frozen plasma, he continued to bleed, although his international normalized ratio improved from 8.8 to 7.2. He underwent hemodialysis, and serum dabigatran concentration decreased from 1,100 to 18 ng/mL over 4 hours, with an initial extraction ratio of 0.97 and blood clearance of 291 mL/min. Although his serum dabigatran concentration rebounded to 100 ng/mL 20 minutes after the cessation of dialysis, his bleeding stopped and he improved clinically. Hemorrhage in the setting of dabigatran anticoagulation remains a therapeutic predicament. Hemodialysis may play an adjunct role in accelerating the elimination of dabigatran in bleeding patients.

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) modified the indications for N-acetylcysteine therapy of acetaminophen (paracetamol) overdose in September 2012. The new treatment threshold line was lowered to 100 mg/L (662 mumol/L) for a 4 hours acetaminophen concentration from the previous 200 mg/L (1325 mumol/L). This decision has the potential to substantially increase overall costs associated with acetaminophen overdose with unclear benefits from a marginal increase in patients protected from hepatotoxicity, fulminant hepatic failure, death, or transplant. Changing the treatment threshold for acetaminophen overdose also implies that ingestion amounts previously thought not to require acetaminophen concentration measurements would need to be revised. As a result, more individuals will be sent to hospitals in order that everyone with a predicted 4 hours concentration above the 100 mg/L line will have concentrations measured and potentially be treated with N-acetylcysteine. Before others consider adopting this new treatment guideline, formal cost-effectiveness analyses need to be performed to define the appropriate thresholds for referral and treatment.

BACKGROUND: Flecainide is a class IC antidysrhythmic primarily indicated for ventricular dysrhythmias and supraventricular tachycardia (SVT). Class IC antidysrhythmic overdose has a reported mortality of 22%, and death results from dysrhythmias and cardiovascular collapse. We report a near-fatal flecainide overdose in an 18-day-old treated successfully with sodium bicarbonate. CASE REPORT: An 18-day-old, 2 weeks premature, 4-kg boy developed persistently high heart rates (220-240 beats/min) and electrocardiographic changes consistent with SVT. There was minimal response to vagal maneuvers, adenosine, and esmolol, and a transthoracic echocardiogram showed no underlying structural abnormality. The patient was then started on flecainide 4 mg orally every 8 h (Q8h). After the fourth dose he developed lethargy, cold clammy skin, and a heart rate of 40 beats/min with no palpable pulse. The patient was given 0.1 mg of atropine intravenously, with an increase of the heart rate to 160 beats/min. The child's cardiac monitor revealed a wide-complex tachycardia with left bundle branch morphology, with associated pallor and poor capillary refill. Sodium bicarbonate was administered intravenously due to suspected flecainide toxicity. Approximately 5 min after intravenous administration of 10 mEq of 8.4% sodium bicarbonate twice, his rhythm converted to a narrow-complex tachycardia. A serum flecainide concentration was 1360 mug/L (therapeutic, 200-1000 mug/L) drawn 1 h before the cardiac arrest. It was later discovered that a twofold dosing error occurred: the patient received 8 mg Q8h instead of 4 mg Q8h for four doses. CONCLUSION: Flecainide toxicity in children is rare, especially in neonates. It is important for clinicians to be able to identify and treat this uncommon poisoning.