Faculty Bibliography

Background: Propoxyphene, an opioid structurally similar to methadone is marketed in combination with acetaminophen or salicylates. Propoxyphene is also a sodiumchannel blocker. Death from propoxyphene overdose may result from respiratory depression or wide-complex dysrhythmias. We report a death from wide-complex dysrhythmia following an intentional propoxyphene/ acetaminophen overdose. Case report: A 37-year-old agitated woman was brought to the ED by EMS. Vital signs: BP, 150/106 mmHg; pulse, 120 beats/min; respirations, 30 breaths/min; room air O2 saturation, 99%. She rapidly became bradycardic with a HR of 40 beats/ min and unresponsive with no measurable blood pressure. CPR and endotracheal intubation were performed, and atropine and epinephrine were given with electrical defibrillation. The systolic BP returned to 40-65 mmHg with a pulse of 30 beats/min. The ECG showed a QRS interval of 180 ms. Sodium bicarbonate, calcium chloride, a glucagon infusion (5 mg/h) and high-dose insulin was administrated without improvement. A transcutaneous pacer was applied but could not capture. Despite high dose infusion of norepinephrine and vasopressin she expired about 4 h later. Tablets of propoxyphene/ acetaminophen were brought in by family and her serum propoxyphene concentration was subsequently reported as 615 ng/mL (200-400 ng/mL). Case discussion: Propoxyphene overdoses are characterized by respiratory depression and sodium channel blockade. Despite significant toxicity, several studies show that propoxyphene's analgesic effect is no better than acetaminophen alone. In 2005, British authorities initiated phased withdrawal of propoxyphene as a result of over 300 deaths/year. In the US since the 1980s, there have been over 2,000 deaths from propoxyphene. At an FDA meeting to determine if propoxyphene should be withdrawn, 14 members voted to withdraw the drug and 12 against withdrawal. Despite this vote, the FDA ultimately decided against withdrawal and recommended a boxed warning about the potential cardiotoxicity. Conclusion: Propoxyphene overdose and fatalities continues to occur in the US. This raises questions about the risk/benefit of this combination product

Objective. Diphenhydramine is an H1 histamine antagonist that is commonly used for allergic reactions, colds and cough, and as a sleep aid. In addition to anticholinergic and antihistaminergic effects, sodium channel blockade becomes evident following diphenhydramine overdose. While seizures may occur following overdose of a diphenhydramine, status epilepticus is distinctly uncommon. We report a case with both status epilepticus and wide-complex dysrhythmias following an intentional diphenhydramine overdose. Case report. A 36-year-old woman with a medical history of hypothyroidism on levothyroxine was brought to the emergency department with active seizures by emergency medical services after what was later determined to be a diphenhydramine overdose. One hour after an argument with her husband he found her lethargic in a locked room. Initial vital signs were: blood pressure, 90/55 mmHg; heart rate, 160 beats/min; respiratory rate 18 breaths/min; room air oxygen saturation, 99%; temperature, 99.8 degrees F; rapid point-of-care glucose, 130 mg/dL. The generalized seizures continued for duration of 30 min, despite the intravenous administration of 8 mg of lorazepam. The patient underwent endotracheal intubation and a propofol infusion terminated her seizures. An electrocardiogram after the status was terminated which revealed a wide-complex tachycardia with QRS duration of 127 ms. The QRS narrowed after 200 mEq of intravenous sodium bicarbonate was administrated. The patient was neurologically intact upon extubation on hospital day 2. The serum diphenhydramine concentration drawn on arrival to the ED was 1200 ng/mL (9-120 ng/mL); a tricyclic screen was negative. Discussion. While seizures and sodium channel blockade are recognized complications of diphenhydramine toxicity, reported cases of status epilepticus from diphenhydramine overdose are rare. Elements of the patient's presentation were similar to a tricyclic overdose and management required aggressive control of her seizures, sodium bicarbonate therapy, and recognizing that physostigmine was contraindicated due to wide complex tachycardia. Conclusions. Diphenhydramine overdose may cause status epilepticus and wide-complex tachycardia. Management should focus on antidotal therapy with sodium bicarbonate and supportive neurological management with appropriate anticonvulsants and airway protection if clinically indicated

Poisoning is the second leading cause of injury-related fatality in the USA and the leading cause of cardiac arrest in victims under 40 years of age. The study objective was to define the electrocardiographic (ECG) predictors of adverse cardiovascular events (ACVE) complicating suspected acute poisoning (SAP). This was a case-control study in adults at three tertiary-care hospitals and one regional Poison Control Center. We compared 34 cases of SAP complicated by ACVE to 101 consecutive control patients with uncomplicated SAP. The initial ECG was analyzed for rhythm, intervals, QT dispersion, ischemia, and infarction. ECGs were interpreted by a cardiologist, blinded to study hypothesis and case data. Subjects were 48% male, with mean age 42 +/- 19 years. In addition to clinical suspicion of poisoning in 100% of patients, routine toxicology screens were positive in 77%, most commonly for benzodiazepines, opioids, and/or acetaminophen. Neither the ventricular rate, the QRS duration, nor the presence of infarction predicted the risk of ACVE. However, the rhythm, QTc, QT dispersion, and presence of ischemia correlated with the risk of ACVE. Independent predictors of ACVE based on multivariable logistic regression were prolonged QTc, any non-sinus rhythm, ventricular ectopy, and ischemia. Recursive partitioning analysis identified very low risk criteria (94.1% sensitivity, 96.2% NPV) and high risk criteria (95% specificity). Among patients with SAP, the presence of QTc prolongation, QT dispersion, ventricular ectopy, any non-sinus rhythm, and evidence of ischemia on the initial ECG are strongly associated with ACVE

The use of race as a risk assessment tool and pharmacologic target has garnered recent attention and debate. It is currently unclear if a relationship between race and the development of severe alcohol withdrawal exists. We explored this potential relationship using several study groups. Methods: A simultaneous prospective enrollment of patients and retrospective chart review of severe alcohol withdrawal in two separate settings was performed comparing both the incidence of withdrawal and alcoholism based on race. These two study groups were then compared to an 'at risk' group of alcoholics and the general ED population to determine differences in the distribution of race. Results: Individuals of white race in both study groups were at increased odds [OR 1.93 (CI 1.11-3.39) and 2.19 (CI 1.41-3.40)] of having severe alcohol withdrawal when compared to non-White 'at risk' alcoholics. Blacks in both study groups however, appear to have lower odds [OR 0.23 (CI 0.11-0.47) and 0.11 (CI 0.05-0.23)] of having severe alcohol withdrawal when compared to non-Black 'at risk' alcoholics. Conclusions: Despite the controversial use of race in medical research and targeting therapies, there appears to be a difference in the odds of severe alcohol withdrawal based on race. The reasons for this finding are currently unclear

We report a case of multisystem organ failure after large volume subcutaneous injection of castor oil for cosmetic enhancement. An unlicensed practitioner injected 500 mL of castor oil bilaterally to the hips and buttocks of a 28-year-old male to female transsexual. Immediate local pain and erythema were followed by abdominal and chest pain, emesis, headache, hematuria, jaundice, and tinnitus. She presented to an emergency department 12 hours postinjection. Persistently hemolyzed blood samples complicated preliminary laboratory analysis. She rapidly deteriorated despite treatment and developed fever, tachycardia, hemolysis, thrombocytopenia, hepatitis, respiratory distress, and anuric renal failure. An infectious diseases evaluation was negative. After intensive supportive care, including mechanical ventilation and hemodialysis, she was discharged 11 days later, requiring dialysis for an additional 1.5 months. Castor oil absorption was inferred from recovery of the Ricinus communis biomarker, ricinine, in the patient's urine (41 ng/mL). Clinicians should anticipate multiple complications after unapproved methods of cosmetic enhancement