Craig G. Smollin

Partition constant and volume of distribution as predictors of clinical efficacy of lipid rescue for toxicological emergencies

Context. Lipid infusion is useful in reversing cardiac toxicity of local anesthetics, and recent reports indicate it may be useful in resuscitation from toxicity induced by a variety of other drugs. While the mechanism behind the utility of lipid rescue remains to be fully elucidated, the predominant effect appears to be creation of a “lipid sink”. Objective. Determine whether the extraction of drugs by lipid, and hence the clinical efficacy of lipid rescue in toxicological emergencies can be predicted by specific drug properties. Materials and methods. Each drug investigated was added individually to human drug-free serum. Intralipid® was added to this drug-containing serum, shaken and then incubated at 37°C. The lipid was removed by ultracentrifugation and the concentration of drug remaining in the serum was measured by high-pressure liquid chromatography. Results. In this in vitro model, the ability of lipid emulsion to bind a drug was largely dependent upon the drugs lipid partition constant. Additionally, using a multiple linear regression model, the prediction of binding could be improved by combining the lipid partition constant with the volume of distribution together accounting for approximately 88% of the variation in the decrease in serum drug concentration with the administration of lipid emulsion. Conclusions. The lipid partition constant and volume of distribution can likely be used to predict the efficacy of lipid infusion in reversing the cardiac toxicity induced by anesthetics or other medications.

Comprehensive analysis of “bath salts” purchased from California stores and the internet

Abstract Study objective. To analyze the contents of “bath salt” products purchased from California stores and the Internet qualitatively and quantitatively in a comprehensive manner. Methods. A convenience sample of “bath salt” products were purchased in person by multiple authors at retail stores in six California cities and over the Internet (U.S. sites only), between August 11, 2011 and December 15, 2011. Liquid chromatography-time-of-flight mass spectrometry was utilized to identify and quantify all substances in the purchased products. Results. Thirty-five “bath salt” products were purchased and analyzed. Prices ranged from

Cardiogenic shock after use of fluoroamphetamine confirmed with serum and urine levels

9.95 to 49.99 (U.S. dollars). Most products had a warning against use. The majority (32/35, 91%) had one (n = 15) or multiple cathinones (n = 17) present. Fourteen different cathinones were identified, 3,4-methylenedioxypyrovalerone (MDPV) being the most common. Multiple drugs found including cathinones (buphedrone, ethcathinone, ethylone, MDPBP, and PBP), other designer amines (ethylamphetamine, fluoramphetamine, and 5-IAI), and the antihistamine doxylamine had not been previously identified in U.S. “bath salt” products. Quantification revealed high stimulant content and in some cases dramatic differences in either total cathinone or synthetic stimulant content between products with the same declared weight and even between identically named and outwardly appearing products. Conclusion. Comprehensive analysis of “bath salts” purchased from California stores and the Internet revealed the products to consistently contain cathinones, alone, or in different combinations, sometimes in high quantity. Multiple cathinones and other drugs found had not been previously identified in U.S. “bath salt” products. High total stimulant content in some products and variable qualitative and quantitative composition amongst products were demonstrated.

Adverse Effects From Counterfeit Alprazolam Tablets.

Abstract Context. 4-Fluoroamphetamine (4-FA) is a para-substituted phenethylamine-type synthetic stimulant that has in recent years gained popularity through internet blogs and market share according to confiscated drug data. No serious toxicity has previously been reported. We report a case of a young man who developed severe toxicity and cardiogenic shock after using 4-FA, with laboratory confirmation. Case details. An 18-year-old man presented to the emergency department with vomiting, shortness of breath, chest tightness, and altered mental status about 5 h after using a new and unfamiliar street drug. Two days prior, he had received naltrexone intramuscular injection as part of an opioid addiction treatment program and was taking fluoxetine and trazodone. Five hours after presentation, he developed cardiogenic shock requiring intraaortic balloon pump, inotropic and ventilatory support. An echocardiogram showed left ventricular (LV) hypokinesia, sparing the apex and ejection fraction (EF) = 10%. Comprehensive toxicology serum testing revealed FA, naproxen, trazodone, and cotinine. The 4-FA urine level was 64,000 ng/ml and serum level was 118 ng/ml. With slow recovery, the patient was discharged after 2 weeks of hospitalization. Discussion. Although no previously reported 4-FA clinical poisoning cases have been published for comparison, by examining 4-FA pharmacology compared with other stimulant drugs, and given this patients presentation and echocardiogram suggestive of reverse takotsubo cardiomyopathy we suspect the toxic mechanism was an acute cardiomyopathy caused by 4-FA catecholamine-induced myocarditis and/or small vessel myocardial ischemia. Conclusion. Recreational use of 4-FA may present with life threatening toxicity including cardiomyopathy, cardiogenic shock, and pulmonary edema.

An observational case series of dabigatran and rivaroxaban exposures reported to a poison control system

Adverse Effects From Counterfeit Alprazolam Tablets From October 15 to December 31, 2015, the California Poison Control System–San Francisco division identified 8 patients who experienced adverse effects associated with the ingestion of counterfeit alprazolam tablets found to contain fentanyl and, in some cases, etizolam. The identification of these patients resulted in a coordinated response that included state and local public health departments, a toxicology laboratory, and media outlets, and resulted in an investigation by local law enforcement agencies.

Publication of Abstracts Presented at 2001 NACCT

OBJECTIVE Characterize clinical presentations and outcomes of dabigatran and rivaroxaban exposures reported to a poison control system. METHODS Data for cases of dabigatran and rivaroxaban exposures called into the California Poison Control System from January 2011 to July 2013 were collected. Data collected included patient demographics, type of exposure, medication, dosage, vital signs, laboratory values, interventions, outcomes, and disposition. Exclusion criteria included confirmed nonexposures or miscoded cases. RESULTS A total of 56 cases were identified, with 7 excluded, leaving 37 dabigatran and 12 rivaroxaban cases. Children age 12 years or less accounted for 5 dabigatran and 2 rivaroxaban cases. Bleeding was reported in 15 dabigatran cases. There were 4 cases of acute self-harm overdose with dabigatran ranging from 1800 to 3900 mg. Mild bleeding was reported in only one of these overdose cases. There were 2 fatal hemorrhages in dabigatran cases, both in chronic therapeutic dosing. Bleeding was reported in 5 rivaroxaban cases, all in patients with chronic exposure; no deaths were reported. There were no adverse outcomes in pediatric patients. Coagulation parameters did not correlate well with bleeding. CONCLUSIONS In our series, the greatest risk of adverse events was in patients chronically taking these agents, irrespective of excess dosing. Acute self-harm ingestions and accidental pediatric ingestions had few adverse effects, although massive overdose can lead to abnormal coagulation studies. It does not appear that single low-dose ingestions of either medication will lead to clinically significant bleeding. It may be possible to manage some pediatric exposures and most accidental ingestions with observation.

Pepper Spray Injury Severity: Ten-year Case Experience of a Poison Control System

IntroductionThe timely and formal publication of material presented as abstracts at national meetings is critical to the dissemination of new information to the medical community. We designed a retrospective study to evaluate the publication rates of abstracts presented at a recent national toxicology conference. In addition, we attempted to determine whether readily identifiable characteristics could predict a greater likelihood of publication.MethodsIn June of 2004, we reviewed 237 abstracts from the 2001 North American Congress of Clinical Toxicology (NACCT). Abstracts were classified according to methodology and content. We then searched Medline, using PubMed, to determine the publication of each abstract.ResultsFifty-seven of 237 abstracts (24.1%) were subsequently published in peer reviewed journals. There was no statistically significant difference in the rate of publication when abstracts were categorized with respect to methodology. When categorized with respect to content, abstracts related to natural toxins had a higher publication rate (41.2%; p < 0.05).ConclusionsThree years after presenting abstracts at the 2001 NACCT meeting, the majority of abstracts remain unpublished. This is a lower rate than noted by other specialty medical societies.

Case Files of the University of California San Francisco Medical Toxicology Fellowship: Lamotrigine Toxicity

Abstract Background. Pepper spray is a common lacrimator used by law enforcement and the public to subdue individuals and for self-defense. The risk factors for severe injury due to pepper spray exposure are not well documented and there is a lack of guidelines to identify patients that require transport and medical evaluation in an emergency department. Objective. The aim of this study was to determine the prevalence of and circumstances associated with symptoms suggestive of tissue injury beyond transient irritation in persons exposed to pepper spray. Methods. We reviewed all human exposures to pepper spray reported to a poison control system between 2002 and 2011. Cases were differentiated into 2 outcome groups: minor or self-limiting symptoms versus those with more severe symptoms suggestive of tissue injury that warranted a medical evaluation. A comparison of the variables between the outcome groups was performed using odds ratios (ORs), 95% confidence intervals (CIs), and associated P values. Results. A total of 4,544 cases were identified and 3,671 met the inclusion criteria. Of these, 249 cases (6.8%) were found to have more severe symptoms that warranted a medical evaluation. There were no reported deaths. The cases with more severe symptoms most commonly involved the ocular (53.8%), respiratory (31.7%), and dermal (17.7%) organ systems. Factors with largest independent associations with more severe outcomes were use for law enforcement training (OR, 7.39; 95% CI, 2.98–18.28), direct intentional exposure for purposeful use to incapacitate (OR, 3.02; 95% CI, 1.80–5.06), and for law enforcement on individual target suspects or crowd control (OR, 2.45; 95% CI, 1.42–4.23). Conclusions. There was a low 1 in 15 potential risk for more severe adverse health effects in persons exposed to pepper spray that warranted a medical evaluation. The risk was highest when used for training of law enforcement personnel and involved severe ocular symptoms. This suggests that routine use of pepper spray for training of law enforcement or military personnel be reconsidered. Protective goggles may be an option when direct spraying into the face of trainees. Transport for medical evaluation should be considered for exposed persons that manifest persistent ocular or respiratory symptoms.

Online social networking and US poison control centers: Facebook as a means of information distribution

A 56-year-old man was brought to the emergency department (ED) after he was found seizing on the floor by his family. His brother described hearing a thump in his room and witnessed him having a full body clonic seizure that lasted approximately 2 min. When emergency medical service arrived, he was found on the floor with altered mental status and with signs of facial trauma. No medications were administered en route to the hospital. On arrival to the ED, he was initially confused and mumbling incoherently. He was noted to be only oriented to self, and would not reliably follow commands. Approximately 1 h after arrival, he became agitated, seemed more confused, and would not follow any commands. Initial vital signs were: blood pressure, 147/76 mmHg; pulse, 81/min; respiratory rate, 18/min; temperature, 35°C by tympanic measurement; and oxygen saturation was 100% on room air. On physical exam, his pupils were 4 mm and reactive bilaterally. Extraocular movements appeared intact by observation only and there was no nystagmus. He had a nasal deformity and laceration to the right side of his tongue. The chest exam was normal with the exception of a large median sternotomy scar. His abdomen was soft, nontender, and there were no signs of bladder distension. Bowel sounds were noted to be present. There was no evidence of bowel or bladder incontinence. The neurological exam was notable for decreased attention, inability to follow commands, inability to repeat examiner’s phrases, and markedly reduced language skills. The patient had spastic muscle tone with resistance to motion both with flexion and extension of all extremities. Deep tendon reflexes were noted to be 2+ in bilateral upper extremities and 3+ in bilateral lower extremities without clonus.

Cannabis Intoxication Case Series: The Dangers of Edibles Containing Tetrahydrocannabinol

Abstract Background. Online social networking services such as Facebook provide a novel medium for the dissemination of public health information by poison control centers in the United States. We performed a cross-sectional study of poison control center Facebook pages to describe and assess the use of this medium. Methods. Facebook pages associated with poison control centers were identified during a continuous two-week period from December 24, 2012 to January 7, 2013. Data were extracted from each page, including affiliated poison control center; page duration, measured in years since registration; number of subscribers; number of postings by general toxicological category; and measures of user-generated activity including “likes”, “shares”, and comments per posting. Results. Among the 56 US poison control centers, 39 Facebook pages were identified, of which 29 were currently active. The total number of active pages has increased by 140% from 2009 to 2013 (average of 25% per year). The total number of all subscribers to active pages was 11,211, ranging from 40 to 2,456 (mean 387, SD 523), equal to 0.006% of all Facebook users in the United States. The number of subscribers per page was associated with page duration, number of postings, and type of postings. The types of toxicological postings were public education (45%), self-promotion (28%), childhood safety (12%), drugs of abuse (8%), environmental poisonings (6%), and general overdoses (1%). Conclusion. Slightly over half of all poison control centers in the United States are supplementing their outreach and education efforts through Facebook. In general, the more active the poison control center on Facebook, the more page followers and follower engagement gained.