Publications by authors named "Anthony F Pizon"

55 Publications

Outcomes Following Naloxone Administration by Bystanders and First Responders.

Prehosp Emerg Care 2021 Apr 19:1-9. Epub 2021 Apr 19.

University of Pittsburgh, Department of Emergency Medicine, Pittsburgh, 15260 United States.

Background: Naloxone is widely available to bystanders and first responders to treat patients with suspected opioid overdose. In these patients, the prognostic factors and potential benefits associated with additional naloxone administered by emergency medical services (EMS) are uncertain.

Objectives: We sought to identify prognostic factors for admission to the hospital following prehospital administration of naloxone for suspected opioid overdose by bystanders and first responders. We secondarily examined whether administration of additional naloxone by paramedics after initial treatment by non-EMS personnel was associated with improvement in level of consciousness prior to hospital arrival.

Methods: This is a retrospective cross-sectional study of patients treated within a single urban EMS system from 2013-2016. Inclusion criteria were administration of naloxone by bystanders or first responders and transport to one of three academic medical centers. For the secondary analysis, only patients with a Glasgow Coma Scale (GCS) score ≤12 on paramedic arrival were included. We performed univariate and multivariable analyses examining a primary outcome of hospital admission and secondary outcome of improvement in consciousness as defined by GCS >12 in patients with initial GCS ≤12.

Results: Of 359 patients identified for the primary analysis, 60 were admitted to the hospital. Factors associated with increased rate of admission included higher total naloxone dosage (OR 1.36, 95%CI 1.09-1.70) and presence of alternate/additional non-opioid central nervous system (CNS) depressants (OR 2.51, 95%CI 1.13-5.56). Among 178 patients who had poor neurologic status (GCS ≤12) on paramedic arrival following naloxone administered by bystander or first responder, administration of additional naloxone was not associated with a better rate of neurologic improvement prior to hospital arrival (77% improved with additional naloxone, 81% improved without additional naloxone; OR 0.82, 95%CI 0.39-1.76).

Conclusions: Among patients with suspected opioid overdose treated with naloxone by bystanders and first responders, a higher total dose of naloxone and polysubstance intoxication with additional CNS depressants were predictors of admission. Administration of additional naloxone by paramedics was not associated with a higher rate of neurologic improvement prior to hospital arrival, suggesting a ceiling effect on naloxone efficacy in opioid overdose.
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http://dx.doi.org/10.1080/10903127.2021.1918299DOI Listing
April 2021

Educating the Educators.

J Med Toxicol 2021 Apr 9;17(2):157-159. Epub 2021 Feb 9.

Rocky Mountain Poison & Drug Safety, Denver, CO, USA.

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http://dx.doi.org/10.1007/s13181-021-00827-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017033PMC
April 2021

Highest reported clearance of valproate by hemodialysis in massive overdose.

Am J Emerg Med 2021 01 16;39:255.e5-255.e6. Epub 2020 Jul 16.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, United States of America.

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http://dx.doi.org/10.1016/j.ajem.2020.06.073DOI Listing
January 2021

Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity.

Clin Toxicol (Phila) 2021 Feb 26;59(2):106-110. Epub 2020 May 26.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: In cases of ethylene glycol (EG) toxicity requiring hemodialysis (HD), fomepizole is dosed every four hours. HD efficiently clears EG and its toxic metabolites, and it's unclear if multiple doses (MD) of fomepizole improve patient outcomes or whether a single dose (SD) prior to initiation of HD is sufficient.

Methods: We reviewed cases of EG toxicity at a toxicology referral center from 2008 to 2018. Patients treated with HD with EG levels greater than 20 mg/dL were included. Duration of dialysis, creatinine at discharge, hospital length of stay (LOS), and complications were analyzed. We compared patients who received a single dose of fomepizole prior to HD to those who received continued dosing during and after HD.

Results: Twenty-five patient encounters were identified (MD: 20; SD: 5). Initial bicarbonate (11 [SD] vs. 9 mg/dL [MD]) and pH (7.1 vs. 7.1) were similar between the groups; however, there was a trend toward a greater proportion of patients with renal dysfunction in the MD group: 11 (55%) vs. 1 (20%). HD was initiated a median interval of 5.2 h [SD] vs. 5.7 h [MD] after a dose of fomepizole. There was one death in the MD group and none in the SD group. Median creatinine on the day of discharge was 0.7 mg/dL (IQR: 0.57-3.8) in the SD group and 2.0 mg/dL (0.90-7.0) in the MD group. LOS was similar (5.8 days [95% CI 3.6-8.0] vs. 7.6 days [5.3-9.9]) ( = .61).

Conclusion: Patients with moderately severe EG toxicity (acidosis and no initial renal dysfunction) treated with a single dose of fomepizole prior to HD had similar outcomes to those receiving continued dosing of fomepizole during or after HD. This raises the possibility that a single dose of fomepizole may be sufficient if HD is initiated quickly.
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http://dx.doi.org/10.1080/15563650.2020.1770780DOI Listing
February 2021

Drug-specific risk of severe QT prolongation following acute drug overdose.

Clin Toxicol (Phila) 2020 Dec 7;58(12):1326-1334. Epub 2020 Apr 7.

Division of Medical Toxicology, Department of Emergency Medicine, Elmhurst Hospital Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose. This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease). From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron. This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.
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http://dx.doi.org/10.1080/15563650.2020.1746330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541562PMC
December 2020

Pulmonary Complications of Opioid Overdose Treated With Naloxone.

Ann Emerg Med 2020 01 8;75(1):39-48. Epub 2019 Jun 8.

Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Study Objective: We aim to determine whether administration of higher doses of naloxone for the treatment of opioid overdose is associated with increased pulmonary complications.

Methods: This was a retrospective, observational, cross-sectional study of 1,831 patients treated with naloxone by the City of Pittsburgh Bureau of Emergency Medical Services. Emergency medical services and hospital records were abstracted for data in regard to naloxone dosing, route of administration, and clinical outcomes, including the development of complications such as pulmonary edema, aspiration pneumonia, and aspiration pneumonitis. For the purposes of this investigation, we defined high-dose naloxone as total administration exceeding 4.4 mg. Multivariable analysis was used to attempt to account for confounders such as route of administration and pretreatment morbidity.

Results: Patients receiving out-of-hospital naloxone in doses exceeding 4.4 mg were 62% more likely to have a pulmonary complication after opioid overdose (42% versus 26% absolute risk; odds ratio 2.14; 95% confidence interval 1.44 to 3.18). This association remained statistically significant after multivariable analysis with logistic regression (odds ratio 1.85; 95% confidence interval 1.12 to 3.04). A secondary analysis showed an increased risk of 27% versus 13% (odds ratio 2.57; 95% confidence interval 1.45 to 4.54) when initial naloxone dosing exceeded 0.4 mg. Pulmonary edema occurred in 1.1% of patients.

Conclusion: Higher doses of naloxone in the out-of-hospital treatment of opioid overdose are associated with a higher rate of pulmonary complications. Furthermore, prospective study is needed to determine the causality of this relationship.
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http://dx.doi.org/10.1016/j.annemergmed.2019.04.006DOI Listing
January 2020

Novel ketamine analogues cause a false positive phencyclidine immunoassay.

Ann Clin Biochem 2019 09 25;56(5):598-607. Epub 2019 Jun 25.

1 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1177/0004563219858125DOI Listing
September 2019

Neurotoxic envenomation by the South African coral snake (Aspidelaps lubricus): A case report.

Toxicon 2019 Mar 17;159:38-40. Epub 2019 Jan 17.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Iroquois Building Suite 400, 3600 Forbes Ave, Pittsburgh, PA 15213, USA. Electronic address:

The South African coral snake (Aspidelaps lubricus, Elapidae) has not previously been reported to cause any neurotoxic envenomations in humans. We recently treated a 44-year-old man who was bitten twice, once in each hand, by a captive South African coral snake (Aspidelaps lubricus) while feeding the female snake who had recently laid eggs. Approximately one hour after receiving the bite, he developed vomiting, respiratory failure requiring mechanical ventilation, and paralysis of the bulbar and upper extremity muscles, with retention of voluntary motor control in the lower extremities. Supportive care was provided, and paralysis and respiratory failure resolved spontaneously 12 hours after onset. No antivenom for this species is available. To our knowledge, this is the first published case report of significant human envenomation by Aspidelaps lubricus. Physicians, first responders, and herpetologists should be aware of the potential for neurotoxicity in humans.
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http://dx.doi.org/10.1016/j.toxicon.2019.01.001DOI Listing
March 2019

The Effect of a Medical Toxicology Inpatient Service in an Academic Tertiary Care Referral Center.

J Med Toxicol 2019 01 23;15(1):12-21. Epub 2018 Oct 23.

University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Introduction: Morbidity and mortality from poison- and drug-related illness continue to rise in the USA. Medical toxicologists are specifically trained to diagnose and manage these patients. Inpatient medical toxicology services exist but their value-based economic benefits are not well established.

Methods: This was a retrospective study where length of stay (LOS) and payments received between a hospital with an inpatient medical toxicology service (TOX) and a similar hospital in close geographic proximity that does not have an inpatient toxicology service (NONTOX) were compared. Controlling for zip code, demographics and distance patients lived from each hospital, we used a fitted multivariate linear regression model to identify factors associated with changes in LOS and payment.

Results: Patients admitted to the TOX center had 0.87 days shorter LOS per encounter and the hospital received an average of $1800 more per patient encounter.

Conclusion: In this study, the presence of an inpatient medical toxicology service was associated with decreased patient LOS and increased reimbursement for admitted patients. Differences may be attributable to improved direct patient care provided by medical toxicologists, but future prospective studies are needed.
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http://dx.doi.org/10.1007/s13181-018-0684-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314930PMC
January 2019

Predictors of resistant alcohol withdrawal (RAW): A retrospective case-control study.

Drug Alcohol Depend 2018 11 2;192:303-308. Epub 2018 Oct 2.

Department of Pharmacy, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, United States; Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace St, Pittsburgh, PA 15213, United States.

Background: Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW).

Methods: A retrospective cohort of adults with severe alcohol withdrawal were screened. Demographic and clinical variables, collected through chart review, underwent logistic regression to select the subset that predicst RAW.

Results: 736 patients (515 nRAW, 221 RAW) were analyzed. RAW patients were younger (P < 0.001), male (P = 0.008) Caucasians (P = 0.037) with histories of psychiatric illness (P < 0.001), higher serum ethanol concentrations (P < 0.007), and abnormal liver enzymes (P = 0.01). RAW patients had significantly lower platelets (P < 0.001), chloride (P = 0.02), and potassium (P = 0.01) levels; severity of illness (SAPSII) (P < 0.001) and comorbidity scores (P < 0.001). Caucasian race and male gender were found to be 3.6 and 2.6 times more likely to be RAW. For every 1-unit increase in comorbidity and severity of illness scores, patients were 22% [OR(95% CI) 0.78 (0.66-0.90)] and 4% [0.96 (0.93-0.98)] less likely to be RAW. Patients with a psychiatric history or thrombocytopenia were 2 times more likely [2.02 (1.24-3.30); 2.13 (1.31-3.50), respectively] to be RAW.

Conclusion: These data demonstrate the predictive ability of a history of psychiatric illness, thrombocytopenia, gender, race, baseline severity of illness and comorbidity scores for developing RAW. Considering these characteristics in early withdrawal management may prevent progression to RAW outcomes.
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http://dx.doi.org/10.1016/j.drugalcdep.2018.08.017DOI Listing
November 2018

Multimodal analgesia in crotalid snakebite envenomation: A novel use of femoral nerve block.

Am J Emerg Med 2018 12 14;36(12):2340.e1-2340.e2. Epub 2018 Sep 14.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh, Iroquois Building Suite 400, 3600 Forbes Ave, Pittsburgh, PA 15213, USA.

Snakebite envenomations occur throughout the United States, with most envenomations resulting from Crotalid bites. These envenomations can result in severe pain despite aggressive analgesia due to effects of venom toxins. We report a case in which we treated a 44- year-old man who sustained a Copperhead (Agkistrodon contortrix) bite to his left hallux with progressive local toxicity, including severe pain radiating into his upper leg, without evidence of compartment syndrome or coagulopathy. His pain was unresponsive to multiple doses of opioids. We performed a fascia iliaca compartment femoral nerve block under dynamic ultrasound guidance with 20 mL of 0.25% bupivacaine, which provided substantial pain relief in his upper leg. To our knowledge, this is a novel application of regional anesthesia with peripheral nerve block. We demonstrate fascia iliaca compartment femoral nerve block may be a safe, beneficial technique for emergency physicians to utilize in providing multimodal analgesia in Crotalid envenomation.
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http://dx.doi.org/10.1016/j.ajem.2018.09.020DOI Listing
December 2018

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

Crit Care Med 2018 08;46(8):e768-e771

Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA.

Objectives: Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal.

Design: Retrospective observational cohort study.

Setting: Academic tertiary care hospital.

Patients: Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria.

Interventions: Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients.

Measurements And Main Results: A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13).

Conclusions: Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.
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http://dx.doi.org/10.1097/CCM.0000000000003204DOI Listing
August 2018

Clinical Outcomes and Mortality Impact of Hyperbaric Oxygen Therapy in Patients With Carbon Monoxide Poisoning.

Crit Care Med 2018 07;46(7):e649-e655

Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA.

Objectives: Carbon monoxide poisoning affects 50,000 per year in the United States alone. Mortality is approximately 3%, and up to 40% of survivors suffer from permanent neurocognitive and affective deficits. Hyperbaric oxygen therapy has shown benefit on reducing the long-term neurologic sequelae of carbon monoxide poisoning but has not demonstrated improved survival. The objective of this study is to assess the efficacy of hyperbaric oxygen for acute and long-term mortality in carbon monoxide poisoning using a large clinical databank.

Design: Retrospective analysis.

Setting: University of Pittsburgh Medical Center healthcare system (Pittsburgh, PA).

Patients: One-thousand ninety-nine unique encounters of adult patients with carbon monoxide poisoning.

Interventions: None.

Measurements And Main Results: Baseline demographics, laboratory values, hospital charge transactions, discharge disposition, and clinical information from charting were obtained from the electronic medical record. In propensity-adjusted analysis, hyperbaric oxygen therapy was associated with a reduction in inpatient mortality (absolute risk reduction, 2.1% [3.7-0.9%]; p = 0.001) and a reduction in 1-year mortality (absolute risk reduction, 2.1% [3.8-0.4%]; p = 0.013).

Conclusions: These data demonstrate that hyperbaric oxygen is associated with reduced acute and reduced 1-year mortality. Further studies are needed on the mortality effects of hyperbaric oxygen therapy in carbon monoxide poisoning.
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http://dx.doi.org/10.1097/CCM.0000000000003135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005724PMC
July 2018

Newly Emerging Drugs of Abuse and Their Detection Methods: An ACLPS Critical Review.

Am J Clin Pathol 2018 Jan;149(2):105-116

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

Objectives: Illicit drug abuse has reached an epidemic level in the United States. Drug overdose has become the leading cause of injury-related deaths since 2008 due to the recent surge of opioid overdose by heroin, controlled prescription drugs, and nonmethadone synthetic opioids. Synthetic designer drugs such as synthetic cathinones ("bath salts") and synthetic cannabinoids ("Spice" and "K2") continue to emerge and attract recreational users.

Methods: The emergence of new drugs of abuse poses a steep challenge for clinical toxicology laboratories. Limited information about the emerging drugs and their metabolism, "rebranding" of the illicit drugs, and a lack of Food and Drug Administration-approved screening methods for these drugs contribute to this difficulty. Here we review detection methods that can aid in identifying emerging drugs of abuse.

Results: One promising approach is the utilization of untargeted drug screening by mass spectrometry. Historically, gas chromatography-mass spectrometry has been the gold standard.

Conclusions: Liquid chromatography-tandem mass spectrometry and liquid chromatography-high-resolution mass spectrometry offer improved detection capability of new drugs with simplified sample preparation, making it the new standard.
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http://dx.doi.org/10.1093/ajcp/aqx138DOI Listing
January 2018

Hypoglycemia and lactic acidosis outperform King's College criteria for predicting death or transplant in acetaminophen toxic patients.

Clin Toxicol (Phila) 2018 07 5;56(7):622-625. Epub 2018 Jan 5.

h Emergency Department , Hamad General Hospital, Hamad Medical Corporation , Doha , Qatar.

Importance: Acetaminophen toxicity is common and is characterized by hepatic failure. In cases that are not improving with standard medical therapy with N-acetylcysteine, some patients may require hepatic transplant. While there are various criteria to predict patients who might benefit from transplant, the King's College criteria remain one of the most widely used. However, the King's College criteria have several limitations and do not incorporate glucose, an important marker of hepatic function.

Objective: The primary objective of this study is to compare the presence of hypoglycemia, coagulopathy, and metabolic acidosis with the King's College criteria for predicting a composite endpoint of death or transplant.

Design: This study is a retrospective cohort study of adult patients admitted with a discharge diagnosis of acetaminophen-induced liver failure.

Setting: The patients were admitted at one of six university-affiliated teaching hospitals in the United States.

Results: A total of 334 subjects were identified who met inclusion criteria. Fifty-one subjects (15.3%) met the composite endpoint of death or transplant. Ninety-six (28.7%) subjects met the King's College criteria for transplant. The presence of hypoglycemia increased the odds of reaching the composite endpoint by 3.39-fold. This model performed better than the King's College criteria (pseudo R for the area under the curve of 0.93 vs. 0.20 for the King's College criteria).

Conclusions: The combination of hypoglycemia, coagulopathy, and lactic acidosis performed better than the King's College criteria for predicting death or transplant.
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http://dx.doi.org/10.1080/15563650.2017.1420193DOI Listing
July 2018

Methemoglobinemia Due to Antifreeze Ingestion.

N Engl J Med 2017 11;377(20):1993-1994

University of Pittsburgh Medical Center, Pittsburgh, PA

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http://dx.doi.org/10.1056/NEJMc1712813DOI Listing
November 2017

Ricin Poisoning after Oral Ingestion of Castor Beans: A Case Report and Review of the Literature and Laboratory Testing.

J Emerg Med 2017 Nov 4;53(5):e67-e71. Epub 2017 Oct 4.

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Clinical Laboratories, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, Pennsylvania; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Clinical Laboratory, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.

Background: Ricin is a protein toxin derived from the castor bean plant Ricinus communis. Several cases secondary to its consumption have been published and, more recently, its use as a potential bioterrorism agent has also been reported. Oral absorption of ricin is highly erratic, leading to a wide spectrum of symptoms. In addition, conventional urine drug screening tests will not be able to detect this compound, posing a diagnostic challenge.

Case Report: A male teenager intended to die by ingesting 200 castor beans after mixing and blending them with juice. Eight hours later, he presented with weakness, light-headedness, nausea, and vomiting and sought medical treatment. The patient was admitted and treated conservatively. An immune-based standard urine toxicology drug screen panel was reported as negative. A comprehensive untargeted urine drug screen test showed the presence of ricinine, a surrogate marker of ricin intoxication. He was transferred to the psychiatric service 3 days after admission. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the importance of knowing the peculiar pharmacokinetic properties of ricin after oral ingestion of castor beans and toxin release through mastication. Emergency physicians should be aware that oral absorption of ricin is dependent on several factors, such type and size of seeds and the geographic harvesting region, making it extremely difficult to estimate its lethality based solely on the number of ingested beans. Finally, comprehensive untargeted urine drug screening testing is highly valuable as a diagnostic tool in this context.
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http://dx.doi.org/10.1016/j.jemermed.2017.08.023DOI Listing
November 2017

Estimating the impact of adopting the revised United Kingdom acetaminophen treatment nomogram in the U.S. population.

Clin Toxicol (Phila) 2017 Jul 1;55(6):569-572. Epub 2017 Mar 1.

j Hamad General Hospital , Hamad Medical Corporation , Doha , Qatar.

Background: Acetaminophen toxicity is common in clinical practice. In recent years, several European countries have lowered the treatment threshold, which has resulted in increased number of patients being treated at a questionable clinical benefit.

Objective: The primary objective of this study is to estimate the cost and associated burden to the United States (U.S.) healthcare system, if such a change were adopted in the U.S.

Methods: This study is a retrospective review of all patients age 14 years or older who were admitted to one of eight different hospitals located throughout the U.S. with acetaminophen exposures during a five and a half year span, encompassing from 1 January 2008 to 30 June 2013. Those patients who would be treated with the revised nomogram, but not the current nomogram were included. The cost of such treatment was extrapolated to a national level.

Results: 139 subjects were identified who would be treated with the revised nomogram, but not the current nomogram. Extrapolating these numbers nationally, an additional 4507 (95%CI 3641-8751) Americans would be treated annually for acetaminophen toxicity. The cost of lowering the treatment threshold is estimated to be $45 million (95%CI 36,400,000-87,500,000) annually.

Conclusions: Adopting the revised treatment threshold in the U.S. would result in a significant cost, yet provide an unclear clinical benefit.
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http://dx.doi.org/10.1080/15563650.2017.1291945DOI Listing
July 2017

A Patient With Alcoholic Ketoacidosis and Profound Lactemia.

J Emerg Med 2016 Oct;51(4):447-449

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Background: Alcoholic ketoacidosis (AKA) is a complex syndrome that results from disrupted metabolism in the setting of excessive alcohol use and poor oral intake. Dehydration, glycogen depletion, high redox state, and release of stress hormones are the primary factors producing the characteristic anion gap metabolic acidosis with an elevated β-hydroxybutyrate (β-OH) and lactate.

Case Report: We present the case of a 47-year-old man who presented to the emergency department with metabolic acidosis and profoundly elevated lactate levels who had AKA. He recovered completely with intravenous fluids and parenteral glucose administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians should always consider the immediately life-threatening causes of a severe anion gap metabolic acidosis and treat aggressively based on the situation. This case highlights the fact that AKA can present with an impressively elevated lactate levels. Emergency physicians should keep AKA in the differential diagnosis of patients who present with a similar clinical picture.
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http://dx.doi.org/10.1016/j.jemermed.2015.05.048DOI Listing
October 2016

Regional variations in pediatric medication exposure: Spatial analysis of poison center utilization in western Pennsylvania.

Clin Toxicol (Phila) 2016 26;54(1):47-52. Epub 2015 Nov 26.

d Department of Epidemiology , Epidemiology Data Center, Graduate School of Public Health, University of Pittsburgh , Pittsburgh , PA , USA.

Context: Medication drug exposures among young children continue to rise despite current poison prevention efforts. These exposures result in increased healthcare utilization and medical costs. New tactics are needed to reduce injuries related to pediatric drug exposures.

Objective: We aimed to identify cluster patterns in: (1) calls for pediatric medication drug exposures and (2) a subset of calls that resulted in medical evaluation referrals. We identified and evaluated population characteristics associated with cluster patterns.

Methods: We analyzed 26,685 pharmaceutical drug exposures involving children <5 years of age based on calls reported to the Pittsburgh Poison Center from 1 January 2006 to 31 December 2010. We performed spatial statistics to assess for clustering. We used logistic regression to estimate population characteristics associated with clustering.

Results: Spatial analysis identified 22 exposure clusters and five referral clusters. Sixty-five percent of 89 ZIP codes in the clusters of drug exposure with healthcare facility (HCF) referral were not identified in the exposure clusters. ZIP codes in the HCF referral clusters were characterized as rural, impoverished, and with high rates of unemployment and school dropouts.

Discussion: Our principal findings demonstrate pediatric drug exposures do exist in discrete geographic clusters and with distinct socioeconomic characteristics.

Conclusion: This study offers a starting point for subsequent investigations into the geographic and social context of pediatric medication drug exposures. This is an important step in revising pediatric poison prevention strategies.
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http://dx.doi.org/10.3109/15563650.2015.1113543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5107113PMC
April 2016

Alcohol Withdrawal Syndrome: Improving Outcomes Through Early Identification And Aggressive Treatment Strategies.

Emerg Med Pract 2015 Jun 1;17(6):1-18; quiz 19. Epub 2015 Jun 1.

Associate Professor, Division of Medical Toxicology, Dept. of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA.

Alcoholism is a prevalent medical and psychiatric disease, and, consequently, alcohol withdrawal is encountered frequently in the emergency department. This issue reviews the pathophysiology of the alcohol withdrawal syndrome, describes the 4 manifestations of alcohol withdrawal, and looks at the available evidence for optimal treatment of alcohol withdrawal in its diverse presentations. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, intravenous benzodiazepines, and, frequently, adjunctive pharmacotherapy. An aggressive front-loading approach with benzodiazepines is proposed and the management of benzodiazepine-resistant disease is addressed.
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June 2015

Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol.

Drug Alcohol Depend 2015 Sep 16;154:296-9. Epub 2015 Jul 16.

Department of Pharmacy, UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace Street, Pittsburgh, PA 15213, USA. Electronic address:

Background: Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW.

Methods: Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use.

Results: Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions.

Conclusions: The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.
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http://dx.doi.org/10.1016/j.drugalcdep.2015.07.005DOI Listing
September 2015

Warfarin overdose: a 25-year experience.

J Med Toxicol 2014 Jun;10(2):156-64

Department of Medical Toxicology, Banner Good Samaritan Medical Center, Phoenix, AZ, USA,

Warfarin, a vitamin K antagonist, is widely used for the prophylaxis and treatment of thromboembolic disease. While guidelines exist for management of a supratherapeutic international normalized ratio following therapeutic warfarin use, these guidelines are not designed for management of the acute warfarin overdose. There is a paucity of literature describing the latter. The primary objective of this manuscript is to characterize the coagulopathy and describe the bleeding events that occur after a warfarin overdose. A secondary goal is to describe the amount of vitamin K administered to patients presenting with warfarin overdoses. A retrospective chart review of patients admitted with an acute warfarin overdose at two tertiary care medical centers in the USA was conducted. Clinical characteristics were abstracted, and bleeding categories (major, minor, trivial) were defined a priori. Twenty-three patients were admitted during the time period; males accounted for 15/23 (62.5 %) subjects. The median (interquartile range (IQR)) age was 43 (32-48.5) years. Seventeen subjects received vitamin K, with a median (IQR) dose of 15 (10-50) mg. The maximal total amount of vitamin K administered to a single patient during the index hospitalization was 110 mg. Three bleeding events occurred; one classified as major, and two as minor. All patients made a full recovery. In this case series of acute warfarin overdose, nearly all patients developed a coagulopathy, and nearly three-quarters of patients received vitamin K. Bleeding events occurred in a minority of patients.
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http://dx.doi.org/10.1007/s13181-013-0378-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057544PMC
June 2014

Complications following antidotal use of intravenous lipid emulsion therapy.

J Med Toxicol 2014 Mar;10(1):10-4

Department of Emergency Medicine, Section of Medical Toxicology, University of Southern California, 1200 North State Street, #1011, Los Angeles, CA, 90033, USA,

The primary objective is to identify and describe the complications associated with the use of intravenous lipid emulsion (ILE) therapy as an antidote for lipophilic drug toxicity. This study is a retrospective chart review of patients treated with ILE at two academic medical centers between 2005 and 2012. Based on previously reported complications, we hypothesized that pancreatitis, ARDS, and lipemia-induced laboratory interference might occur. Clinical definitions of these complications were defined a priori. Subjects treated with ILE who did not develop at least one complication were excluded. A total of nine patients were treated with ILE during the study period, six of whom experienced potential complications as a result of the ILE. Two patients developed pancreatitis, and four patients had lipemia-induced interference of interpretation of laboratory studies, despite ultracentrifugation. Laboratory interference precluded one patient from being an organ donor. Three patients developed ARDS; although temporally associated, a causal relationship between ILE and the development of ARDS cannot be clearly established. As ILE is increasingly used for less severe cases of drug toxicity, clinicians should be aware of potential complications associated with its use. A risk-benefit assessment for the use of ILE should be implemented on a case-by-case basis.
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http://dx.doi.org/10.1007/s13181-013-0356-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951645PMC
March 2014

Prosthetic hip-associated cobalt toxicity.

J Med Toxicol 2013 Dec;9(4):416-7

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA,

Prosthetic hip-associated cobalt toxicity (PHACT) is gaining recognition due to the use of metal-on-metal total hip replacements. Identifying true toxicity from merely elevated cobalt levels can be extremely difficult due to the lack of available data. An extensive review of the medical literature was undertaken to characterize cobalt toxicity from prosthetic hips. As an objective approach to making the diagnosis of PHACT, we suggest the following criteria: (1) elevated serum or whole blood cobalt levels due to a prosthetic hip, (2) at least two test-confirmed findings consistent with cobalt toxicity, and (3) exclusion of other etiologies. Adhering to objective diagnostic data for PHACT is a realistic and prudent method by which to eliminate the subjectivity of vague or difficult to identify complaints. These diagnostic criteria are not meant to evaluate prosthetic hardware failure, but as a means to identify systemic cobalt toxicity. Finally, assessment of cobalt toxicity from prosthetic hips should be done in conjunction with a medical toxicologist.
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http://dx.doi.org/10.1007/s13181-013-0321-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846969PMC
December 2013

Phosgene exposure: a case of accidental industrial exposure.

J Med Toxicol 2014 Mar;10(1):51-6

Division of Medical Toxicology, Department of Emergency Medicine, University of Virginia School of Medicine, PO Box 800774, Charlottesville, VA, 22908-0774, USA,

Introduction: Phosgene is a rare exposure with strong clinical implications. We report a phosgene exposure that resulted in the patient's death.

Case Report: A 58 year-old man arrived to the emergency department 1 hour after exposure to phosgene with complaints of a sore throat. Initial vital signs were blood pressure 175/118 mmHg, heart rate 98/min, respirations 12/min, and oxygen saturation of 93% on room air. Physical exam revealed few scattered rhonchi, without signs of distress. Initial arterial blood gases (ABG's) revealed pH 7.42, pCO2 43 mmHg, pO2 68 mmHg, HCO3 27 meq/L, and oxygen saturation of 93% on room air. Initial chest x-ray 2 hours after the exposure demonstrated clear lung fields. Approximately 2.5 hours after the exposure, he began complaining of dyspnea, restlessness and his oxygen saturation dropped below 90%. He received nebulized albuterol, 1 gram intravenous methylprednisolone, and 100 % oxygen via face mask. Minimal improvement was noted and he was intubated. The post intubation chest x-ray, 3.5 hours after the exposure, revealed diffuse alveolar infiltrates. Acetylcysteine, terbutaline, and IV steroids were administered without improvement. The patient died 30 hours after exposure.

Discussion: There are many misunderstandings concerning phosgene due to its rare presentation. Traditional treatment modalities are often unproven in human trials and were unsuccessful in this case.

Conclusion: This case highlights the significant toxicity that results from phosgene exposure and the challenges of the limited treatment modalities. There is concern for the use of this agent in chemical terrorism.
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http://dx.doi.org/10.1007/s13181-013-0319-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951639PMC
March 2014

Pygmy rattlesnake envenomation treated with Crotalidae Polyvalent Immune Fab Antivenom.

Toxicon 2012 Dec 30;60(7):1287-9. Epub 2012 Aug 30.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, PUH South Tower, Suite M2935, Pittsburgh, PA 15213, USA.

Unlabelled: Documented envenomations by the pygmy rattlesnake (Sistrurus miliarius barbouri) are rare. While there have been no documented fatalities, several older case reports describe significant morbidity. We describe the first known case of pygmy rattlesnake envenomation that was treated with Crotalidae Polyvalent Immune Fab Antivenom (CroFab®).

Case: A 28-year-old man with no significant past medical history presented after being envenomated on the right hand by his friend's pet pygmy rattlesnake. He developed swelling and pain in his hand and forearm. He responded well to a ten vial loading dose and a 18 h maintenance protocol of CroFab and was discharged the following day without developing any hematological or electrolyte derangements.

Conclusion: This is the first documented use of CroFab for S. m. barbouri envenomation. The outcome of this case suggests that CroFab is a safe treatment modality in this setting.
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http://dx.doi.org/10.1016/j.toxicon.2012.08.007DOI Listing
December 2012

Nonfatal tramadol overdose may cause false-positive phencyclidine on Emit-II assay.

Am J Emerg Med 2013 Feb 31;31(2):444.e5-9. Epub 2012 Aug 31.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

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http://dx.doi.org/10.1016/j.ajem.2012.05.028DOI Listing
February 2013

4-aminopyridine toxicity: a case report and review of the literature.

J Med Toxicol 2012 Sep;8(3):314-21

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center, PUH South Tower, Suite M2935, Pittsburgh, PA 15213, USA.

Introduction: 4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert-Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose.

Case Report: A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully.

Discussion: The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose.
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http://dx.doi.org/10.1007/s13181-012-0248-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550165PMC
September 2012