Faculty Bibliography

Objective. Dabigatran is a direct thrombin inhibitor approved for anticoagulation in non-valvular atrial fibrillation and, in some countries, for thromboembolism prophylaxis following select orthopedic surgeries. Despite decreased rates of thromboembolism, bleeding remains a risk due to the inability to conveniently monitor anticoagulant effect and the lack of a reversal agent. Case series. We present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin, clopidogrel, and dabigatran presented with rectal bleeding and epistaxis. He died despite transfusion and administration of prothrombin complex concentrate. A 73-year-old woman on dabigatran and aspirin survived after transfusion and an emergent sternotomy for cardiac tamponade. An 86 year-old man with kidney disease and thrombocytopenia received packed red blood cells, platelets, and fresh frozen plasma for rectal bleeding while on dabigatran. An 80 year-old man on dabigatran had a subdural hematoma after falling and hitting his head. Serial imaging showed no progression. Conclusion. The absence of a reversal agent for dabigatran raises concern for uncontrollable bleeding and death. Dabigatran's listed contraindications include active bleeding and a history of dabigatran hypersensitivity reaction. Wider use may result in bleeding rates higher than anticipated from clinical trials. Risks factors that may have contributed to bleeding in these patients include concomitant bleeding diathesis, antiplatelet agent use, renal insufficiency, advanced age, and fall risks.

Although alcohol use has long been a significant cause of hospital presentations, little is published regarding the long-term demographic changes that have occurred at a single hospital site. To address this deficit, we prospectively studied all acute alcohol-related presentations to Bellevue Hospital Center (New York, NY) and compared this contemporary data set with one from the same institution from 1902 to 1935. We prospectively identified all patients presenting to the emergency department because of acute alcohol use over an 8-week period in 2009. We described the basic attributes of patients presenting currently because of alcohol and compared these data to those previously described between 1902 and 1935. We also compared our census data with contemporaneous data from all patients presenting to this hospital site. During the study period, 560 patients presented because of acute alcohol use which extrapolated to an estimated 3,800 patients over the calendar year. This compares to 7,600 presentations recorded annually early in the twentieth century. Twelve percent of patients in 2009 were female as compared to 18 % of patients between 1934 and 1935. Patients with alcohol-related presentations in 2009 were more likely to be admitted than contemporaneous patients without an alcohol-related presentation (30 vs. 19 % admitted; p < 0.001). Since first measured 110 years ago at one large New York City hospital, alcohol-related presentations remain common representing 5 % of all emergency department visits. This demonstrates alcoholism's continuing toll on society's limited medical resources and on public health as a whole.

BACKGROUND: The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatment (ECTR) in poisoning. To test and validate its methods, the workgroup reviewed data for thallium (Tl). METHODS: After an extensive search, the co-chairs reviewed the articles, extracted the data, summarized findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Blinded votes were compiled, returned, and discussed during a conference call. A second vote determined the final recommendations. RESULTS: Forty-five articles met inclusion criteria. Only case reports and case series were identified, yielding a very low quality of evidence for all recommendations. Data on 74 patients, including 11 who died, were abstracted. The workgroup concluded that Tl is slightly dialyzable and made the following recommendations: ECTR is recommended in severe Tl poisoning (1D). ECTR is indicated if Tl exposure is highly suspected on the basis of history or clinical features (2D) or if the serum Tl concentration is >1.0 mg/L (2D). ECTR should be initiated as soon as possible, ideally within 24-48 hours of Tl exposure (1D), and be continued until the serum Tl concentration is <0.1 mg/L for a minimal duration of 72 hours (2D). CONCLUSION: Despite Tl's low dialyzability and the limited evidence, the workgroup strongly recommended extracorporeal removal in the case of severe Tl poisoning.

ACADEMIC EMERGENCY MEDICINE 2012; 19:843-849 (c) 2012 by the Society for Academic Emergency Medicine ABSTRACT: Objectives: Drug overdose is a leading cause of cardiac arrest and is currently the second leading cause of overall injury-related fatality in the United States. Despite these statistics, the incidence of adverse cardiovascular events (ACVEs) in emergency department (ED) patients following acute drug overdose is unknown. With this study, we address the 2010 American Heart Association Emergency Cardiovascular Care update calling for research to characterize the incidence of in-hospital ACVE following drug overdose. Methods: This was a prospective cohort study at two tertiary care hospitals over 12 months. Consecutive adult ED patients with acute drug overdose were prospectively followed to hospital discharge. The main outcome was occurrence of in-hospital ACVE, defined as the occurrence of one or more of the following: myocardial injury, shock, ventricular dysrhythmia, and cardiac arrest. Results: There were 459 ED patients with suspected drug overdose, of whom 274 acute drug overdose qualified and were included for analysis (mean [+/-SE] age = 40.3 [+/-1.0] years; 63% male). Hospital course was complicated by ACVE in 16 patients (some had more than one): 12 myocardial injury, three shock, two dysrhythmia, and three cardiac arrest. The incidence of ACVE was 5.8% overall (95% confidence interval [CI] = 3.6% to 9.3%) and 10.7% (95% CI = 6.6% to 16.9%) among inpatient admissions, with all-cause mortality at 0.7% (95% CI = 0.2% to 2.6%). Conclusions: Based on this study of adult patients with acute drug overdose, ACVE may occur in up to 9.3% overall and up to 16.9% of hospital admissions. Implications for the evaluation and triage of ED patients with acute drug overdose require further study with regard to optimizing interventions to prevent adverse events.

Background: ED treatment of acute opioid withdrawal (OW) is controversial and challenging. Methadone is commonly used for opioid maintenance and detoxification. Although unstudied, it is also used in low dose at our hospital for acute OW. Objectives: This observational study quantifies the subjective and objective effects of intramuscular (IM) methadone in OW. Methods: A convenience sample of adult, Englishspeaking patients who received IM methadone for OW in a large urban public hospital ED were prospectively enrolled and assessed with four parameters: vital signs; the Clinical Opiate Withdrawal Scale (COWS), a validated OW rating system (scores range from 0-47) the Altered Mental Status Scale (AMSS; scores sedation and agitation from )4 to 4); the Withdrawal Symptoms Scale (WSS), a Likert scale (range )2 [severe withdrawal] to +2 [high]). Patients were assessed prior to methadone and at fixed intervals for 2 hours or until discharge. The ordering physician independently assessed OW symptoms using the WSS. Adverse events, oxygen saturation <95%, respiratory rate <12/ min, or CNS depression (AMSS score <=)2) were recorded. A paired Student's t-test was used to calculate significance. Results: Of 77 patients enrolled, 2 did not meet all inclusion criteria. 50 had two or more assessments for comparison. Their average age was 39 (range 21-59), 70% were male, and 74% were in police custody. 38% used methadone alone; 16% heroin alone; 4% oxycodone alone; and the rest used multiple opioids. The average dose of IM methadone was 10.3 mg (range 5- 20 mg); all but 3 patients received 10 mg. The mean COWS score before receiving IM methadone was 11.19 (range 3-23), compared to 4.83 (range 0-20) 30 minutes after methadone (p < 0.001; mean difference = )6.36; 95% CI = )4.57 to )8.15). The mean WSS before and after methadone was )1.54 (range )1 to )2) and )0.755 (range )2 to 2), respectively (p < 0.001; 95% CI = )1.0 to )0.57). The mean physician-assessed WSS was significantly lower than the patient's own assessment by 0.78 (p < 0.001). Adverse events included an asthmatic patient with bronchospasm whose oxygen saturation decreased from 95% to 88% after receiving methadone, a patient whose oxygen saturation decreased from 95% to 93%, and two patients whose AMSS decreased from )1 to )2 (indicating moderate sedation). Conclusion: Low dose IM methadone effectively ameliorates OW with minimal adverse effects

Abstract Extracorporeal treatments (ECTRs), such as hemodialysis and hemoperfusion, are used in poisoning despite a lack of controlled human trials demonstrating efficacy. To provide uniform recommendations, the EXTRIP group was formed as an international collaboration among recognized experts from nephrology, clinical toxicology, critical care, or pharmacology and supported by over 30 professional societies. For every poison, the clinical benefit of ECTR is weighed against associated complications, alternative therapies, and costs. Rigorous methodology, using the AGREE instrument, was developed and ratified. Methods rely on evidence appraisal and, in the absence of robust studies, on a thorough and transparent process of consensus statements. Twenty-four poisons were chosen according to their frequency, available evidence, and relevance. A systematic literature search was performed in order to retrieve all original publications regardless of language. Data were extracted on a standardized instrument. Quality of the evidence was assessed by GRADE as: High = A, Moderate = B, Low = C, Very Low = D. For every poison, dialyzability was assessed and clinical effect of ECTR summarized. All pertinent documents were submitted to the workgroup with a list of statements for vote (general statement, indications, timing, ECTR choice). A modified Delphi method with two voting rounds was used, between which deliberation was required. Each statement was voted on a Likert scale (1-9) to establish the strength of recommendation. This approach will permit the production of the first important practice guidelines on this topic.

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that was previously used in both animals and humans to treat inflammatory conditions and cancer. Levamisole has been identified as a cocaine adulterant in the United States since 2003. By 2009, the United States Drug Enforcement Administration (DEA) estimated that 69% of the cocaine seized contained levamisole. The first case reports of complications related to levamisole in cocaine users were published in 2009. The objectives of this article are to review the literature regarding the full spectrum of possible complications related to levamisole use for medical purposes, to review the current scope of levamisole-induced complications in cocaine users and to discuss the pharmacological properties that might explain the motivation behind the large-scale adulteration of cocaine with levamisole. Literature review revealed that significant complications were quickly reported when levamisole was used in inflammatory conditions. By 1976, several cases of leukopenia and agranulocytosis were reported. Recurrence with re-exposure was well described and agranulocytosis spontaneously reversed upon discontinuation of therapy. Vasculitis secondary to levamisole treatment was first reported in 1978 and mostly manifests as leukocytoclastic vasculitis, cutaneous necrotising vasculitis and thrombotic vasculopathy without vasculitis. These findings typically, but not invariably, involve the ear lobes. Discontinuation of levamisole therapy was again a critical part of the treatment. Various neurological side effects were described with levamisole therapy, the most concerning complication being multifocal inflammatory leukoencephalopathy (MIL). Literature review identified 203 unique cases of complications in cocaine users that can be attributed to levamisole adulteration. The two principal complications reported are haematological (140 cases of neutropenia) and dermatological (84 cases). Even though these complications can occur in isolation, many cases displayed both simultaneously. No formal case of leukoencephalopathy in the setting of cocaine use has been reported so far. A striking phenomenon is the apparent high level of recurrence (27.1%) of symptoms in cocaine users after re-exposure to cocaine that is presumably adulterated. The importance of accurately identifying levamisole-induced complications is therefore critical for symptomatic patients as discontinuation of exposure is fundamental and as a correct diagnosis prevents unnecessary and potentially dangerous use of other treatment modalities like powerful immunosuppressive therapy. Literature review suggests that levamisole might have the advantages of enhancing noradrenergic neurotransmission by inhibiting reuptake, by inhibiting MAO and/or COMT, by acting on ganglionic nicotinic receptors and by being partially metabolized into an amphetamine-like compound. It could also increase endogenous opioids and increase dopamine concentration in the cerebral reward pathway. These potential effects make levamisole an interesting choice as a cocaine adulterant. It seems unlikely that levamisole use as a cocaine adulterant will soon reach an end. More information is needed about the diagnosis and treatment of levamisole-induced complications, and the efforts of the medical and public health community is needed to face this challenging problem.