Robert S Hoffman

Publications of Robert S Hoffman

• Response to: "Intravenous fat emulsion therapy: Can it be tried without sufficient first-line treatment modalities?"

  Authors: Zhanna Livshits, Robert S Hoffman

  Basic & clinical pharmacology & toxicology. 04/2012;

• Wolf spider envenomation.

  Authors: Zhanna Livshits, Benjamin Bernstein, Louis N Sorkin, Silas W Smith, Robert S Hoffman

  Wilderness & environmental medicine. 03/2012; 23(1):49-50.

  Although wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. TheAlthough wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. The infrequent nature of exposure and inherent difficulty in confirming wolf spider bites in humans makes it challenging to study such envenomations. We present the case of a 20 year-old man with confirmed exposure to the wolf spider who developed cutaneous erythema with ulceration following the bite. There was no evidence of skin necrosis. He was treated with aggressive wound care and systemic antibiotics for wound infection, with subsequent resolution of symptoms. This case adds to the limited knowledge regarding wolf spider envenomations and describes the clinical effects and management of wolf spider envenomation.

• Preparing for Chemical Terrorism: A Study of the Stability of Expired Pralidoxime (2-PAM).

  Authors: Robert S Hoffman, Maria Mercurio-Zappala, Nicole Bouchard, Padinjarekuttu Ravikumar, Lewis Goldfrank

  Disaster medicine and public health preparedness. 11/2011;

  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 shelfObjectives: 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.

• Comment: "Quantitative insulin and C peptide levels among ED patients with sulfonylurea-induced hypoglycemia".

  Authors: Zhanna Livshits, Robert S Hoffman

  The American journal of emergency medicine. 09/2011; 29(7):812-3.

• Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.

  Authors: Zhanna Livshits, Simon Lee, Robert S Hoffman, Lewis S Nelson, Nora Esteban-Cruciani

  Clinical toxicology (Philadelphia, Pa.). 08/2011; 49(8):747-9.

  Pediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resultingPediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly prescribed medication to treat HIV-exposed newborns, with limited overdose data in this patient population. Metabolic acidosis with elevated lactate is the most serious consequence of AZT toxicity in the adult population, associated with mortality. Other significant effects may include neutropenia and hepatic dysfunction. A 4-day-old male infant who received two inadvertent 10-fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The newborn developed a transient metabolic acidosis with elevated lactate that resolved within 24 h, a small increase in AST, and persistent neutropenia for 5 weeks. The patient's mother cited several key factors leading to the dosing error. The paucity of AZT overdose data in newborns and infants compels this case report, which reviews the published literature and provides insight into prevention and improvement of pediatric patient safety.

• Adolescents and young adults presenting to the emergency department intoxicated from a caffeinated alcoholic beverage: a case series.

  Authors: Kelly Cleary, Deborah A Levine, Robert S Hoffman

  Annals of emergency medicine. 08/2011; 59(1):67-9.

  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 toWe 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.

• Amlodipine toxicity vs. exposure in children.

  Authors: Daniel M Lugassy, Jennifer A Martin, Robert S Hoffman

  The Journal of emergency medicine. 08/2011; 41(2):187-8.

• Response to effect of deferasirox on iron absorption in a randomized, placebo-controlled, crossover study in a human model of acute supratherapeutic iron ingestion.

  Authors: Amay Parikh, David H Jang, Robert S Hoffman, Mary Ann Howland

  Annals of emergency medicine. 08/2011; 58(2):219-20; author reply 220.

• Heavy metal chelation in neurotoxic exposures.

  Authors: David H Jang, Robert S Hoffman

  Neurologic clinics. 08/2011; 29(3):607-22.

  Metals such as iron and copper are critical to living organisms, whereas other metals such as lead and arsenic have no known biologic role. Any metals in large amounts may cause toxicity. Many metalsMetals such as iron and copper are critical to living organisms, whereas other metals such as lead and arsenic have no known biologic role. Any metals in large amounts may cause toxicity. Many metals cause pervasive systemic effects involving the nervous system, which can be subtle in some cases. Although challenging, the diagnosis and treatment of metal poisoning can be made based on history, physical examination, and the proper use of metal testing. This article focuses on the use, and misuse, of chelation in the diagnosis and management of metal intoxication.

• Life-threatening bupropion ingestion: is there a role for intravenous fat emulsion?

  Authors: Zhanna Livshits, Qi Feng, Farhana Chowdhury, Tshering D Amdo, Lewis S Nelson, Robert S Hoffman

  Basic & clinical pharmacology & toxicology. 07/2011; 109(5):418-22.

  Intravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from someIntravenous fat emulsion (IFE) is emerging as a novel antidote in clinical toxicology. Its current usage is extending beyond local anaesthetic toxicity into management of severe toxicity from some lipophilic drugs. We present a 51-year-old woman with severe bupropion toxicity whose haemodynamic status transiently improved after IFE. Serum analysis demonstrated an increase in serum concentration of hydroxybupropion, an active metabolite of bupropion, after IFE administration, lending support to one of the proposed mechanisms of IFE. A 51-year-old woman presented to the emergency department with generalised tonic-clonic convulsions lasting approximately 30 sec., and a wide complex rhythm on her ECG that was suggestive of myocardial sodium channel blockade. Despite sodium bicarbonate therapy, the patient developed profound hypotension refractory to high-dose norepinephrine. IFE was administered with haemodynamic improvement over the course of 30 min., followed by a significant decrease in norepinephrine requirement. The patient had an episode of ventricular tachycardia 24 hr after presentation, and received a second infusion of IFE. Analysis of serum for a panel of myocardial sodium channel blocking drugs revealed that significant bupropion ingestion had occurred. Bupropion poisoning may produce life-threatening clinical effects, and IFE may be considered in cases of severe haemodynamic instability. Further studies would be instrumental in determining the optimal clinical situations for utilisation of IFE.

• CTA and cocaine-associated chest pain: more evidence is needed.

  Authors: Zhanna Livshits, Robert S Hoffman

  Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 07/2011; 18(7):771; author reply 772-3.

• Validation of a 6-hour observation period for cocaine body stuffers.

  Authors: Zhanna Livshits, Delbert Clark, Miguel Gutierrez, Robert S Hoffman

  The American journal of emergency medicine. 06/2011; 29(5):566.

• Prognostic utility of serum potassium in chronic digoxin toxicity: a case-control study.

  Authors: Alex F Manini, Lewis S Nelson, Robert S Hoffman

  American journal of cardiovascular drugs : drugs, devices, and other interventions. 06/2011; 11(3):173-8.

  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 toIn 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. 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). 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 5.0 mEq/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. 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.

• Methylene blue in the treatment of refractory shock from an amlodipine overdose.

  Authors: David H Jang, Lewis S Nelson, Robert S Hoffman

  Annals of emergency medicine. 05/2011; 58(6):565-7.

  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 releaseAmlodipine 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.

• Fatal outcome of a propoxyphene/acetaminophen (Darvocet) overdose: should it still be used in the United States?

  Authors: David H Jang, Robert S Hoffman, Lewis S Nelson, Jason Chu, Kavita Bhanot, William Bagley

  Annals of emergency medicine. 04/2011; 57(4):421-2.

• Medical examiner and medical toxicologist agreement on cause of death.

  Authors: Alex F Manini, Lewis S Nelson, Dean Olsen, David Vlahov, Robert S Hoffman

  Forensic science international. 03/2011; 206(1-3):71-6.

  Poisoning is a significant public health threat as the second leading cause of injury-related death in the US. Disagreements on cause of death determination may have widespread implications acrossPoisoning is a significant public health threat as the second leading cause of injury-related death in the US. Disagreements on cause of death determination may have widespread implications across several realms of public health including policy and prevention efforts, interpretation of the poisoning literature, epidemiologic data analysis, medical-legal case outcomes, and individualized autopsy interpretation. We aimed to test agreement between the cause of death determined by the medical examiner (ME) and a medical toxicologist (MT) adjudication panel (MTAP) in cases of poisoning. This retrospective 7-year study evaluated all deaths attributed to poisoning in one large urban catchment area. Cross-matched data were obtained from Department of Vital Statistics and the Poison Control Center (PCC). Out of >380,000 deaths in the catchment area over the study period, there were 7050 poisonings in the Vital Statistics database and 414 deaths reported to PCC. Cross-matching yielded 321 cases for analysis. The ME and MTAP concurred on cause of death in 66%, which was only fair agreement (κ 0.25, CI 0.14-0.38). Factors associated with the likelihood of agreement were peri-mortem fire exposures, prehospital cardiac arrest, and timing of drug toxicity (chronic versus acute). In conclusion, agreement for poisoning cause of death between specialties was much lower than expected. We recommend an improved formal process of information sharing and consultation between specialties to assure that all existing information is analyzed thoroughly to enhance cause of death certainty.

• If vitamins could kill: massive hemolysis following naturopathic vitamin infusion.

  Authors: Zhanna Livshits, Robert S Hoffman, Kenneth B Hymes, Lewis S Nelson

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 02/2011; 7(3):224-6.

  Hemolysis from naturopathic remedies remains poorly reported in the medical literature, although it is most commonly noted in the patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. WeHemolysis from naturopathic remedies remains poorly reported in the medical literature, although it is most commonly noted in the patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. We report a case of massive intravascular hemolysis following the infusion of a naturopathic preparation that contains vitamins. A 47-year-old African-American man presented to the hospital with 3 days of fever, dyspnea, emesis, dark urine, and progressive confusion. His symptoms began 1 day following an infusion of a vitamin complex. His physical examination was significant for lethargy and scleral icterus. Initial laboratory studies were notable for anemia (hemoglobin, 3.3 g/dL and hematocrit, 11%), brisk reticulocytosis (33%), acute renal insufficiency (creatinine, 2.8 mg/dL), and indirect hyperbilirubinemia (total bilirubin, 4.4 mg/dL). His peripheral smear demonstrated "blister cells," erythrocytes that have been left devoid of precipitated hemoglobin by the spleen, which are commonly seen in patients with G6PD deficiency. His physician revealed that the infusion contained vitamins B and D complex, free amino acids, magnesium, and taurine. The patient clinically improved and was discharged to home. G6PD concentration was significantly reduced to 4.7 U/g Hb upon recovery. Life-threatening intravascular hemolysis may occur following a naturopathic vitamin infusion and may identify previously unknown G6PD deficiency. Since most properly formulated naturopathic treatments have few toxic ingredients, the possibilities of improper formulation, toxic diluents, or contaminants should be considered. Inadequate regulatory oversight of naturopathic remedies has the potential to allow serious toxicity especially in genetically predisposed individuals.

• Letter to the Editor regarding the published study "Deaths involving serotonergic drugs".

  Authors: Zhanna Livshits, Robert S Hoffman

  Forensic science international. 12/2010; 207(1-3):e62.

• Attempted suicide, by mail order: Abrus precatorius.

  Authors: David H Jang, Robert S Hoffman, Lewis S Nelson

  Journal of medical toxicology : official journal of the American College of Medical Toxicology. 12/2010; 6(4):427-30.

  Abrus precatorius is cultivated in many subtropical areas. The seeds exist in a variety of colors such as black, orange, and most commonly, glossy red. A black band is found at the end of the seed.Abrus precatorius is cultivated in many subtropical areas. The seeds exist in a variety of colors such as black, orange, and most commonly, glossy red. A black band is found at the end of the seed. The plant contains multiple pods which typically contain three to five Abrus seeds. The seeds contain abrin, which inhibits ribosomal function, halting protein synthesis and leading to cellular death. A unique aspect of this case is the use of the internet to order a potentially lethal poison as well as transmission of a picture to identify the seed. A 20-year-old man presented to the emergency department complaining of vomiting and watery diarrhea for 6-8 h prior to arrival. He denied any medication use, recent illness, travel, or changes in his diet. Initial vital signs were normal. The patient was diagnosed with viral gastroenteritis. During his evaluation, the patient admitted to feeling suicidal. While awaiting psychiatry evaluation, the patient's father arrived with a box of small hard red seeds, which he believed that his son ingested in a suicide attempt. The seeds could not be identified by the staff. A picture of the seeds was transmitted by e-mail to the New York City Poison Control Center, allowing their identification as A. precatorius. The patient was reinterviewed and admitted to chewing and swallowing 10 seeds. Given the potential toxicity of abrin, the patient was admitted to the intensive care unit. He continued to have frequent episodes of emesis as well as diarrhea. He gradually improved over 2 days. He admitted to ordering a box of Abrus seeds online from Asia after reading on the Internet about their use in suicide. He was eventually discharged for outpatient follow-up with no permanent sequelae. Abrin has an estimated human fatal dose of 0.1-1 μg/kg. Most cases of Abrus seed ingestions are unintentional and occur in children. Ingesting the intact seeds typically results in no clinical findings, as they pass through the gastrointestinal tract due to their hard shell. Abrin released during chewing is poorly absorbed systemically from the gastrointestinal tract. This causes the vomiting and diarrhea with resultant hypovolemia and electrolyte disturbances, which can be severe and life threatening, particularly in areas with less advanced health care systems. Management is primarily supportive.

• Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose.

  Authors: David H Jang, Alex F Manini, Nathan S Trueger, Danny Duque, Nestor B Nestor, Lewis S Nelson, Robert S Hoffman

  Clinical toxicology (Philadelphia, Pa.). 11/2010; 48(9):945-8.

  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, sodiumDiphenhydramine 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. 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°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. 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. 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.