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Wiener S.W.,SUNY Downstate Medical Center | Wiener S.W.,Kings County Hospital Center | Wiener S.W.,New York City Poison Control Center
Emergency Medicine Clinics of North America | Year: 2014

Acid-base disorders may complicate the presentation of patients with poisoning. This article summarizes an approach to acid-base disorders from a toxicologic perspective. It aims to assist the reader in identifying underlying acid-base processes, generating a differential diagnosis for each, and approaching that differential diagnosis in a systematic fashion. Understanding these processes will help to guide management and interventional strategies. © 2014 Elsevier Inc.


Takematsu M.,Yeshiva University | Hoffman R.S.,New York University | Nelson L.S.,New York University | Nelson L.S.,New York City Poison Control Center | And 5 more authors.
Clinical Toxicology | Year: 2014

Case report. A 33-year-old man with no significant medical history presented at the emergency department with right-sided weakness and aphasia. He had smoked a synthetic cannabinoid (SC) product called "WTF" prior to the onset of symptoms. Physical examination showed right hemiparesis, dysarthria, and aphasia. Laboratory evaluation, electrocardiography, and computed tomography (CT) of the head were unremarkable. Following administration of intravenous tissue plasminogen activator, his symptoms improved. A repeat head CT showed acute infarction in the left insular cortex. His hypercoagulability panel was unremarkable, and the patient was discharged neurologically intact. Urine toxicology results were unremarkable. Analysis of the product by gas chromatography-mass spectrometry (GC-MS) procedure confirmed the presence of a synthetic cannabinoid known as XLR-11.Conclusion. XLR-11 has previously been associated with acute kidney injury in humans. However, there are no reports of it causing acute cerebral ischemic events. The close temporal association between XLR-11 inhalation and his stroke is concerning. Acute cerebral infarction may occur after XLR-11 use in healthy patients.Objective. Synthetic cannabinoids are increasingly used in the United States as marijuana substitutes. However, reports of severe toxicity, resulting from their use, are limited. We present the case of acute cerebral infarction following synthetic cannabinoid inhalation. Copyright © 2014 Informa Healthcare USA, Inc.


Nelson L.S.,New York City Poison Control Center | Hoffman R.S.,New York City Poison Control Center
American Journal of Cardiovascular Drugs | Year: 2011

Objective: In contrast to patients with acute digoxin overdose, the prognostic utility of the serum potassium concentration for patients with chronic digoxin toxicity is unclear. In such patients, we aimed to evaluate the relationship between pre-treatment serum potassium and survival. Methods: This was a case-control study at an urban Poison Control Center affiliated with a large urban medical center. We compared the serum potassium concentration between patients with chronic digoxin toxicity resulting in fatality (cases) over a 7-year period (2000-2006) versus survivors (controls) over a 1-year period (2007-2008). Results: During the study period, there were 13 fatalities (cases) and 13 survivors (controls), of whom seven cases and five controls received appropriately dosed digoxin-specific antibody Fab fragments (Fab). There were no statistically significant differences between cases and controls with respect to serum digoxin concentration, creatinine, age, or sex. Serum potassium elevation pre-Fab was significantly associated with fatality both in mean difference (p < 0.03) and using a dichotomous cutoff of 5.0mEq/L (p < 0.001), which performed with 92% sensitivity (95% CI 67, 99). In 86% of deaths despite appropriate Fab administration, the clinical presentation included the combination of bradycardia plus hyperkalemia. Conclusion: In these patients with chronic digoxin toxicity, elevated serum potassium was associated with fatality. The combination of bradycardia and hyperkalemia strongly predicted fatality even in cases with appropriate Fab administration. © 2011 Adis Data Information BV. All rights reserved.


Smith S.W.,New York University | Smith S.W.,New York City Poison Control Center | Hauben M.,Pfizer | Hauben M.,New York University | And 3 more authors.
Drug Safety | Year: 2012

A paradoxical drug reaction constitutes an outcome that is opposite from the outcome that would be expected from the drugs known actions. There are three types: 1. A paradoxical response in a condition for which the drug is being explicitly prescribed. 2. Paradoxical precipitation of a condition for which the drug is indicated, when the drug is being used for an alternative indication. 3. Effects that are paradoxical in relation to an aspect of the pharmacology of the drug but unrelated to the usual indication.In bidirectional drug reactions, a drug may produce opposite effects, either in the same or different individuals, the effects usually being different from the expected beneficial effect. Paradoxical and bidirectional drug effects can sometimes be harnessed for benefit; some may be adverse. Such reactions arise in a wide variety of drug classes. Some are common; others are reported in single case reports. Paradoxical effects are often adverse, since they are opposite the direction of the expected effect. They may complicate the assessment of adverse drug reactions, pharmacovigilance, and clinical management. Bidirectional effects may be clinically useful or adverse. From a clinical toxicological perspective, altered pharmacokinetics or pharmacodynamics in overdose may exacerbate paradoxical and bidirectional effects. Certain antidotes have paradoxical attributes, complicating management. Apparent clinical paradoxical or bidirectional effects and reactions ensue when conflicts arise at different levels in self-regulating biological systems, as complexity increases from subcellular components, such as receptors, to cells, tissues, organs, and the whole individual. These may be incompletely understood. Mechanisms of such effects include different actions at the same receptor, owing to changes with time and downstream effects; stereochemical effects; multiple receptor targets with or without associated temporal effects; antibody-mediated reactions; three-dimensional architectural constraints; pharmacokinetic competing compartment effects; disruption and non-linear effects in oscillating systems, systemic overcompensation, and other higher-level feedback mechanisms and feedback response loops at multiple levels. Here we review and provide a compendium of multiple class effects and individual reactions, relevant mechanisms, and specific clinical toxicological considerations of antibiotics, immune modulators, antineoplastic drugs, and cardiovascular, CNS, dermal, endocrine, musculoskeletal, gastrointestinal, haematological, respiratory, and psychotropic agents. © 2012 Adis Data Information BV. All rights reserved.


Hoffman R.S.,New York City Poison Control Center | Mercurio-Zappala M.,New York City Poison Control Center | Bouchard N.,Columbia University | Ravikumar P.,Public Health Laboratories | Goldfrank L.,New York City Poison Control Center
Disaster Medicine and Public Health Preparedness | Year: 2012

Objectives: Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. Methods: Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 × 150-mm, 5-μm column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. Results: Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N-methyl pyridinium carboxaldehyde degradation product. Conclusions: When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM. © 2012 American Medical Association.


Cleary K.,New York University | Cleary K.,Bellevue Hospital Center | Levine D.A.,New York University | Levine D.A.,Bellevue Hospital Center | And 3 more authors.
Annals of Emergency Medicine | Year: 2012

We describe a case series of emergency department (ED) visits for intoxication related to the use of the caffeinated alcoholic beverage Four Loko. Medical records from the 4-month period July to November 2010 were hand searched for key words such as "intoxicated," "caffeinated," "Four Loko," "alcohol," and "EtOH." Patients were included if they were younger than 25 years. Eleven cases were included. Eight (72.7%) patients presented during October 2010. The median age was 16.4 years; 90.9% were under the legal drinking age of 21 years. Seven (63.6 %) were male patients. All arrived by emergency medical services (EMS). Four patients (36.3%) were found in high-risk settings, with altered mental status on subway tracks, in public buildings, or parks after dark. Two patients had blood alcohol concentrations greater than 200 mg/dL. Six patients (54.5%) had emesis. Two patients (18.2%) were admitted to hospital, 1 each because of seizures and persistent tachycardia. Patients intoxicated with Four Loko were younger than the legal drinking age, found in high-risk situations, and often admitted to the hospital. Many of these patients used EMS and resources in the ED for alleviation of adverse effects of Four Loko. © 2011 American College of Emergency Physicians.


Smith S.W.,New York University | Smith S.W.,New York City Poison Control Center | Smith S.W.,Bellevue Hospital Center
Journal of Medical Toxicology | Year: 2013

These proceedings will review the role of chelation in five metals-aluminum, cadmium, chromium, cobalt, and uranium-in order to illustrate various chelation concepts. The process of "chelation" can often be oversimplified, leading to incorrect assumptions and risking patient harm. For chelation to be effective, two critical assumptions must be fulfilled: the presumed "metal toxicity" must correlate with a given body or a particular compartment burden, and reducing this compartmental or the body burden (through chelation) attenuates toxicity. Fulfilling these assumptions requires an established dose-response relationship, a validated, reproducible means of toxicity assessment (clinical, biochemical, or radiographical), and an appropriate assessment mechanisms of body or compartment burden. While a metal might "technically" be capable of chelation (and readily demonstrable in urine or feces), this is an insufficient endpoint. Clinical relevance must be affirmed. Deferoxamine is an accepted chelator for appropriately documented aluminum toxicity. There is a very minimal treatment window in order to address chelation in cadmium toxicity. In acute toxicity, while no definitive chelation benefit is described, succimer (DMSA), diethylenetriaminepentaacetate (DTPA), and potentially ethylenediaminetetraacetic acid (EDTA) have been considered. In chronic toxicity, chelation is unsupported. There is little evidence to suggest that currently available chromium chelators are efficacious. Similarly, scant human evidence exists with which to provide recommendation for cobalt chelation. DTPA has been recommended for cobalt radionuclide chelation, although DMSA, EDTA, and N-acetylcysteine have also been suggested. DTPA is unsupported for uranium chelation. Sodium bicarbonate is currently recommended, although animal evidence is conflicting. © 2013 American College of Medical Toxicology.


Shy B.D.,Mount Sinai School of Medicine | Portelli I.,New York University | Nelson L.S.,New York University | Nelson L.S.,New York City Poison Control Center
American Journal of Emergency Medicine | Year: 2011

Objectives: We evaluated the frequency that emergency medicine house staff report use of stimulants and sedatives to aid in shift work and circadian transitions. Methods: We surveyed residents from 12 regional emergency medicine programs inviting them to complete a voluntary, anonymous electronic questionnaire regarding their use of stimulants and sedatives. Results: Out of 485 eligible residents invited to participate in the survey, 226 responded (47% response frequency). The reported use of prescription stimulants for shift work is uncommon (3.1% of respondents.) In contrast, 201 residents (89%) report use of caffeine during night shifts, including 118 residents (52%) who use this substance every night shift. Eighty-six residents (38%) reported using sedative agents to sleep following shift work with the most common agents being anti-histamines (31%), nonbenzodiazepine hypnotics such as zolpidem (14%), melatonin (10%), and benzodiazepines (9%). Conclusion: Emergency medicine residents report substantial use of several classes of hypnotics to aid in shift work. Despite anecdotal reports, use of prescription stimulants appears rare, and is notably less common than use of sedatives and non-prescription stimulants. © 2011 Elsevier Inc. All rights reserved.


Hernandez S.H.,New York City Poison Control Center | Hernandez S.H.,New York University | Nelson L.S.,New York City Poison Control Center | Nelson L.S.,New York University
Clinical Pharmacology and Therapeutics | Year: 2010

The emergence of clinically efficacious prescription drugs to treat pain, anxiety, and learning disorders is accompanied by the potential for nonmedical use. Prescription drug abuse has become a modern-day epidemic in the United States and is now second only to marijuana use across all age groups. This article reviews the various data collection, analysis, and reporting systems that have been developed in response to the growing concern for nonmedical prescription drug use. The terminology used to categorize prescription drugs that are abused and the various definitions for abuse, misuse, and nonmedical use are discussed. The epidemiology of nonmedical prescription drug use and an overview of each class of prescription drug that is at risk for nonmedical use are presented along with details of specific drugs that are associated with significant morbidity or mortality. © 2010 American Society for Clinical Pharmacology and Therapeutics.


Jang D.H.,New York University | Jang D.H.,New York City Poison Control Center | Nelson L.S.,New York University | Nelson L.S.,New York City Poison Control Center | And 2 more authors.
Annals of Emergency Medicine | Year: 2011

Amlodipine is a potent vasodilator with a long half-life and delayed onset of action that is particularly concerning after an overdose. Vasodilation occurs through stimulation of nitric oxide release with increased cyclic guanosine monophosphate (cGMP) production. Methylene blue inhibits guanylate cyclase. This enzyme is responsible for the production of cGMP. Methylene blue also has the ability to scavenge nitric oxide, as well as inhibit nitric oxide synthase. We report the use of methylene blue for refractory shock in a patient with amlodipine toxicity. © 2011 American College of Emergency Physicians.

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