Showing papers in "Journal of Medical Toxicology in 2013"

2C or Not 2C: Phenethylamine Designer Drug Review

Abstract: New groups of synthetic “designer drugs” have increased in popularity over the past several years. These products mimic the euphoric effects of other well-known illicit drugs but are advertised as “legal” highs and are sold over the internet, at raves and night clubs, and in head shops. The 2C series drugs are ring-substituted phenethylamines that belong to a group of designer agents similar in structure to 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy). Understanding the pharmacology and toxicology of these agents is essential in order to provide the best medical care for these patients. This review focuses on the pharmacology, pharmacokinetics, clinical effects, and treatment of 2C drug intoxication based on available published literature. Multiple names under which 2C drugs are sold were identified and tabulated. Common features identified in patients intoxicated with 2Cs included hallucinations, agitation, aggression, violence, dysphoria, hypertension, tachycardia, seizures, and hyperthermia. Patients may exhibit sympathomimetic symptoms or symptoms consistent with serotonin toxicity, but an excited delirium presentation seems to be consistent amongst deaths attributed to 2C drugs; at least five deaths have been reported in the literature in patients intoxicated with 2C drugs. 2C drugs are a group of designer intoxicants, many of which are marketed as legal, but may carry risks that consumers are unaware of. These drugs may be characterized by either serotonergic toxicity or a sympathomimetic toxidrome, but a presentation consistent with excited delirium is consistent amongst the reported 2C-related deaths. Treatment of 2C intoxication is primarily supportive, but immediate action is required in the context of excited delirium, hyperthermia, and seizure activity.

The clinical and forensic toxicology of Z-drugs.

Abstract: The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1–7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Z-drugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography–mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

In the Zzz zone: the effects of Z-drugs on human performance and driving.

Abstract: Despite their improved pharmacokinetic profile, the Z-drugs, zolpidem, zopiclone, and zaleplon, have a spectrum of adverse effects comparable to benzodiazepines. This review focuses on the impairment from Z-drugs on cognition, behavior, psychomotor performance, and driving ability. Z-drugs are short-acting GABA agonists that reduce sleep latency without disturbing sleep architecture. Bizarre behavioral effects have prompted warnings on the prescription, dispensation, and use of Z-drugs. Psychomotor impairment, falls, and hip fractures are more likely to occur with Z-drugs that have longer half-lives, that are taken at higher-than-recommended doses and when mixed with other psychoactive substances including alcohol. Zopiclone and higher doses of zolpidem are more likely to cause anterograde amnesia than zaleplon. Z-drugs, especially zolpidem, are associated with complex behaviors such as sleepwalking, sleep-driving, and hallucinations. Patients taking zopiclone and zolpidem have an increased risk of motor vehicle collisions, over double that of unexposed drivers. Driving impairment occurs with zopiclone and higher doses of zolpidem but is unlikely to occur after 4 h post-zaleplon administration. The residual effect of Z-drugs on next-day cognitive and psychomotor performance has significant impact on lifestyle, safety, and occupational considerations, including motor vehicle and machine operation. The risk–benefit analysis of Z-drugs in the treatment of insomnia, particularly in the elderly, may not favor treatment due to the increased risks of falls and motor vehicle collisions. Prescribers should warn patients taking Z-drugs of minimum time thresholds before they operate machinery or drive motor vehicles.

The Effect of Curcumin on Oxaliplatin and Cisplatin Neurotoxicity in Rats: Some Behavioral, Biochemical, and Histopathological Studies

Abstract: Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10–40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.

The Role of Chelation in the Treatment of Arsenic and Mercury Poisoning

Abstract: Chelation for heavy metal intoxication began more than 70 years ago with the development of British anti-lewisite (BAL; dimercaprol) in wartime Britain as a potential antidote the arsenical warfare agent lewisite (dichloro[2-chlorovinyl]arsine). DMPS (unithiol) and DMSA (succimer), dithiol water-soluble analogs of BAL, were developed in the Soviet Union and China in the late 1950s. These three agents have remained the mainstay of chelation treatment of arsenic and mercury intoxication for more than half a century. Animal experiments and in some instances human data indicate that the dithiol chelators enhance arsenic and mercury excretion. Controlled animal experiments support a therapeutic role for these chelators in the prompt treatment of acute poisoning by arsenic and inorganic mercury salts. Treatment should be initiated as rapidly as possible (within minutes to a few hours), as efficacy declines or disappears as the time interval between metal exposure and onset of chelation increases. DMPS and DMSA, which have a higher therapeutic index than BAL and do not redistribute arsenic or mercury to the brain, offer advantages in clinical practice. Although chelation following chronic exposure to inorganic arsenic and inorganic mercury may accelerate metal excretion and diminish metal burden in some organs, potential therapeutic efficacy in terms of decreased morbidity and mortality is largely unestablished in cases of chronic metal intoxication.

Methylene blue for distributive shock: a potential new use of an old antidote.

Abstract: Methylene blue is used primarily in the treatment of patients with methemoglobinemia. Most recently, methylene blue has been used as a treatment for refractory distributive shock from a variety of causes such as sepsis and anaphylaxis. Many studies suggest that the nitric oxide–cyclic guanosine monophosphate (NO–cGMP) pathway plays a significant role in the pathophysiology of distributive shock. There are some experimental and clinical experiences with the use of methylene blue as a selective inhibitor of the NO–cGMP pathway. Methylene blue may play a role in the treatment of distributive shock when standard treatment fails.

The Role of Chelation in the Treatment of Other Metal Poisonings

Abstract: 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.

Clinical Features, Testing, and Management of Patients with Suspected Prosthetic Hip-Associated Cobalt Toxicity: a Systematic Review of Cases

Abstract: Safety concerns regarding cobalt-containing metal alloy hip prosthetics (Co-HP) have resulted in product recalls, a medical device alert, and issuance of guidance for clinicians. Recently, cases of suspected prosthetic hip-associated cobalt toxicity (PHACT) from Co-HP have been reported. Although little is known about suspected PHACT, these patients may be referred to medical toxicologists for evaluation and management recommendations. We searched MEDLINE, EMBASE, and unpublished abstracts from toxicology scientific meetings for references relevant to PHACT. Authors independently screened publications for inclusion criteria: publication in English, human study population, subject(s) are symptomatic (except for isolated hip pain), and cobalt values in any matrix (blood, serum, urine, CSF, synovial fluid) available for review. Data from 10 cases are reviewed. Patients with suspected PHACT had findings consistent with cobalt toxicity, including thyroid, cardiac, and neurologic dysfunction. Signs and symptoms appeared between 3 and 72 months after arthroplasty (median 19 months). Neurologic symptoms were most common. Ancillary testing varied considerably. All patients had elevated cobalt levels in one or more matrices. Enhanced elimination was attempted in 27 % of patients. At this time, the information currently available regarding patients with suspected PHACT is inadequate to guide clinical decision making. No consensus has been reached regarding the management of Co-HP patients with systemic symptoms. Indications for chelation have not been established and require further study. Improved case definitions, improved surveillance, and controlled studies are needed to elucidate the scope of this problem and guide future investigations.

Fentanyl-associated Fatalities Among Illicit Drug Users in Wayne County, Michigan (July 2005–May 2006)

Abstract: Background During the summer of 2005, multiple cities in the United States began to report outbreaks of fentanyl-associated fatalities among illicit drug users The objectives of this study were to (1) determine if an outbreak of fentanyl-associated fatalities occurred in mid-2005 to mid-2006 and (2) to examine trends and compare features of fentanyl-contaminated heroin-associated fatalities (FHFs) with non-fentanyl, heroin-associated fatalities (NFHFs) among illicit drug users

High Times, Low Sats: Diffuse Pulmonary Infiltrates Associated with Chronic Synthetic Cannabinoid Use

Abstract: Introduction In recent years, cases of severe adverse effects from recreational use of synthetic cannabinoids (SC) have established that these agents represent a novel toxicologic hazard.

Leveraging social networks for toxicovigilance.

Abstract: The landscape of drug abuse is shifting. Traditional means of characterizing these changes, such as national surveys or voluntary reporting by frontline clinicians, can miss changes in usage the emergence of novel drugs. Delays in detecting novel drug usage patterns make it difficult to evaluate public policy aimed at altering drug abuse. Increasingly, newer methods to inform frontline providers to recognize symptoms associated with novel drugs or methods of administration are needed. The growth of social networks may address this need. The objective of this manuscript is to introduce tools for using data from social networks to characterize drug abuse. We outline a structured approach to analyze social media in order to capture emerging trends in drug abuse by applying powerful methods from artificial intelligence, computational linguistics, graph theory, and agent-based modeling. First, we describe how to obtain data from social networks such as Twitter using publicly available automated programmatic interfaces. Then, we discuss how to use artificial intelligence techniques to extract content useful for purposes of toxicovigilance. This filtered content can be employed to generate real-time maps of drug usage across geographical regions. Beyond describing the real-time epidemiology of drug abuse, techniques from computational linguistics can uncover ways that drug discussions differ from other online conversations. Next, graph theory can elucidate the structure of networks discussing drug abuse, helping us learn what online interactions promote drug abuse and whether these interactions differ among drugs. Finally, agent-based modeling relates online interactions to psychological archetypes, providing a link between epidemiology and behavior. An analysis of social media discussions about drug abuse patterns with computational linguistics, graph theory, and agent-based modeling permits the real-time monitoring and characterization of trends of drugs of abuse. These tools provide a powerful complement to existing methods of toxicovigilance.

A Review of Emergency Cardiopulmonary Bypass for Severe Poisoning by Cardiotoxic Drugs

Abstract: Cardiovascular collapse remains a leading cause of death in severe acute drug intoxication. Commonly prescribed medications such as antidysrhythmics, calcium channel antagonists, and beta adrenergic receptor antagonists can cause refractory cardiovascular collapse in massive overdose. Emergency cardiopulmonary bypass (ECPB), a modality originating in cardiac surgery, is a rescue technique that has been successfully implemented in the treatment of refractory cardiogenic shock and cardiac arrest unresponsive to traditional medical interventions. More recently a growing number of animal studies, case reports, and case series have documented its use in refractory hemodynamic collapse in poisoned patients. This article will review current ECPB techniques and explore its growing role in the treatment of severely hemodynamically compromised poisoned patients.

A Fatal Case of Thallium Toxicity: Challenges in Management

Abstract: Background Thallium is a highly toxic compound and is occasionally involved in intentional overdoses or criminal poisonings. Accidental poisonings also occur, but are increasingly rare owing to restricted use and availability of thallium. We report a fatal suicidal ingestion of thallium sulfate rodenticide in which multi-dose activated charcoal (MDAC) and Prussian Blue (PB) were both used without changing the outcome.

Acute Psychosis Associated with Recreational Use of Benzofuran 6-(2-Aminopropyl)Benzofuran (6-APB) and Cannabis

Abstract: Introduction There is evidence from around Europe of the availability and use of 6-(2-aminopropyl)benzofuran (6-APB) as a recreational drug. However, there is currently limited information on the acute toxicity of this compound. We describe here a case of acute toxicity associated with recreational use of legal high (6-APB) and cannabis, in which the comprehensive toxicological analysis confirmed the presence of a significant amount of 6-APB together with metabolites of both tetrahydrocannabinol and the synthetic cannabinoid receptor agonist (JWH-122).

“Bath Salts” and “Plant Food” Products: the Experience of One Regional US Poison Center

Abstract: Abuse of psychogenic substances sold as “bath salts” and “plant food” has escalated in recent years in the United States (USA) Previous reports suggest regional differences in the primary active β-keto phenylalkylamines found in these products and the corresponding signs and symptoms reported after exposure Currently, there are only limited studies describing the clinical effects associated with reported “bath salts” exposure in the USA This study describes the clinical effects associated with “bath salt” and “plant food” exposures as reported to the poison center serving the state of North Carolina (Carolinas Poison Center) We performed a retrospective review of the Carolinas Poison Center database for all cases of reported human exposure to “bath salt” and “plant food” products from 2010 to 2011 with specific attention to clinical effects and routes of exposure Additionally, we reviewed therapies used, trended the volume of exposure cases reported over the study period, and evaluated the distribution of calls within state counties using descriptive statistics Carolinas Poison Center received 485 total calls and 409 reported exposure calls regarding “bath salt” or “plant food” products between January of 2010 and December of 2011 The peak of reported exposures occurred in May of 2011 Clinical effects commonly reported in the exposure cases generated from these calls included tachycardia (533 %, n = 218), agitated/irritable (504 %, n = 206), hallucination/delusions (267 %, n = 109), and hypertension (252 %, n = 103) In addition to intravenous fluids, common therapies included benzodiazepines (460 %, n = 188), sedation (134 %, n = 55), alkalinization (390 %, n = 16), antihistamine (416 %, n = 17), and intubation (367 %, n = 15) Haloperidol was the antipsychotic agent used most often to treat agitation (n = 40) Serious complications associated with reported exposure to “bath salt” and “plant food” products included rhabdomyolysis, renal failure, excited delirium syndrome, and death While treatments have not been empirically determined, sedation with benzodiazepines, aggressive cooling for hyperthermic patients, and use of small doses of antipsychotics for choreoathetoid movements not controlled with benzodiazepines are not likely to be harmful

Reliability of postmortem fentanyl concentrations in determining the cause of death.

Abstract: Introduction Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death.

Paraquat poisonings in France during the European ban: experience of the Poison Control Center in Marseille.

Abstract: Paraquat, a widely used herbicide in the world, has caused severe and fatal poisonings. Because of its high toxicity, the European Union withdrew paraquat from its market in July 2007. The purpose of this report is to describe cases of paraquat poisoning recorded at the Poison Control Center in Marseille over the 9-year period starting and ending 4.5 years before and after the paraquat ban. Data analysis showed that the most severe exposures were linked to ingestion. The fatality rate of deliberate consumption was near 50 % (34 suicide attempts and 15 deaths). Our data showed a marginal decline in total number of poisonings observed after the paraquat ban (38 vs 33 after the ban) mostly due to a decrease in the number of unintentional exposure (21 vs 16 after the ban). However, there was no apparent change in the number suicidal attempts using paraquat. Regarding geographical distribution, data showed that most poisonings in mainland France were unintentional, while poisonings in overseas French territories were mostly voluntary. Despite the European ban and the preventive measures, paraquat continues to contribute to severe and life-threatening poisonings in Southeastern and overseas France.

Recurrent seizures and serotonin syndrome following "2C-I" ingestion.

Abstract: The phenethylamines, including 2, 5 dimethoxy-4-iodophenethylamine, commonly referred to as 2C-I, have recently emerged as a new class of designer drugs. Cases of toxicity from these drugs are not well described in the literature. This case report describes a 19 year-old male who insufflated 2C-I. Following the ingestion, the patient developed recurrent seizures, and was taken to the emergency department, where he was noted to be hyperadrenergic and had recurrent seizures. The patient was diagnosed with serotonin syndrome and experienced prolonged respiratory failure, although he ultimately made a full recovery. Comprehensive drug testing revealed the presence of 2C-I. The pharmacologic properties of 2C-I are also discussed.

Positive outcome after intentional overdose of dabigatran.

Abstract: Introduction Dabigatran (Pradaxa™), an orally active direct thrombin inhibitor, was approved by the United States Food and Drug Administration for the prevention of stroke in patients with atrial fibrillation in October 2010. Life-threatening consequences from dabigatran therapy include hemorrhage and bleeding complications, but they typically occur after renal impairment. We describe the first case report of intentional, acute overdose with dabigatran.

Metformin-associated lactic acidosis (MALA): case files of the Einstein Medical Center medical toxicology fellowship.

Abstract: A 39-year-old man presented to the emergency department after intentionally ingesting 50 tablets of metformin 1,000 mg The reported time of ingestion was 6 h prior to arrival Vital signs were: temperature, 374 °C; pulse, 94 beats per minute; blood pressure, 117/74 mmHg; respirations, 16/min; and oxygen saturation, 96 % on room air Gastric lavage was performed, and a single dose of activated charcoal was given His initial serum lactate was 43 mmol/L (normal0067–18 mmol/L) The patient had a negative urine drug screen, and acetaminophen and salicylate levels were below detection limits The patient was admitted for monitoring of lactic acidosis Twenty hours after arrival, the patient became hypotensive with a blood pressure of 85/45 mmHg Arterial blood gas analysis revealed a pH of 720, pCO2 19 mmHg, and bicarbonate HCO3 of 6 mmol/L A repeat serum lactate at this time was 20 mmol/L, and a basic metabolic panel showed sodium of 134 mmol/L, potassium 38 mmol/L, chloride 98 mmol/L, bicarbonate 16 mmol/L, BUN 32 mg/ dL, and creatinine 13 mg/dL; the calculated anion gap was 20 mmol/L A 1-L normal saline bolus was administered, and serum alkalinization was initiated with a sodium bicarbonate drip The nephrology service was consulted to perform emergent hemodialysis (HD) The patient subsequently underwent two HD treatments of 4-h duration each Following dialysis, the serum pH continued to decrease to 67 The patient became unresponsive and was intubated for airway protection The hypotension persisted despite fluid resuscitation and bicarbonate therapy Norepinephrine and vasopressin drips were started in conjunction with continuous veno-venous hemofiltration (CVVH) With introduction of CVVH, the bicarbonate drip was discontinued The lactate level increased to greater than 30 mmol/L (upper limit of the lab’s reporting range) Forty-eight hours after arrival, the serum pH was 70, and the patient remained hypotensive despite continued vasopressor drips and CVVH

Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

Abstract: Sodium bicarbonate is central to the treatment of many poisonings. When it was placed on the FDA drug shortage list in 2012, alternative treatment strategies to specific poisonings were considered. Many hospital pharmacies, poison centers, and medical toxicologists proposed sodium acetate as an adequate alternative, despite a paucity of data to support its use in medical toxicology. The intention of this review is to educate the clinician on the use of sodium acetate and to advise them on the potential adverse events when given in excess. We conducted a literature search focused on the pharmacology of sodium acetate, its use as a buffer in pathologic acidemia and dialysis baths, and potential adverse events associated with excess sodium acetate infusion. It appears safe to replace sodium bicarbonate infusion with sodium acetate on an equimolar basis. The metabolism of acetate, however, is more complex than bicarbonate. Future prospective studies will be needed to confirm the efficacy of sodium acetate in the treatment of the poisoned patient.

Case files of the University of California San Francisco Medical Toxicology Fellowship: acute chlorine gas inhalation and the utility of nebulized sodium bicarbonate.

Abstract: On a sunny California day in August, the San Francisco Poison Control Center (PCC) received a call from paramedics that a previously healthy 3-year-old girl had possibly been exposed to chlorine gas at a neighborhood swimming pool. The Fire Department later confirmed that both a 10– 16 % sodium hypochlorite solution and a 15 % hydrochloric acid solution were used for pool cleaning that day. The patient was sitting near an outflow jet in the children’s pool, and her mother noticed a sudden increase in bubbles from the jet accompanied by a noxious odor. The mother promptly removed the patient from the pool and estimated an exposure time of approximately 45 s.

Current Use of Chelation in American Health Care

Abstract: The National Center for Health Statistics estimates that more than 100,000 Americans receive chelation each year, although far fewer than 1 % of these cases are managed by medical toxicologists Unfortunately, fatalities have been reported after inappropriate chelation use There are currently 11 FDA-approved chelators available by prescription although chelation products may also be obtained through compounding pharmacies and directly over the internet Promotion of chelation training is prominent on some alternative and complementary medicine websites

Opioid Receptor Polymorphism A118G Associated with Clinical Severity in a Drug Overdose Population

Abstract: Genetic variations in the human mu-opioid receptor gene (OPRM1) mediate individual differences in response to pain and opiate addiction. We studied whether the common A118G (rs1799971) mu-opioid receptor single nucleotide polymorphism (SNP) was associated with overdose severity in humans. In addition, we examined an SNP responsible for alternative splicing of OPRM1 (rs2075572). We assessed allele frequencies of the above SNPs and associations with clinical severity in patients presenting to the emergency department (ED) with acute drug overdose. This work was designed as an observational cohort study over a 12-month period at an urban teaching hospital. Participants consisted of consecutive adult ED patients with suspected acute drug overdose for whom discarded blood samples were available for analysis. Specimens were linked with clinical variables (demographics, urine toxicology screens, clinical outcomes) then deidentified prior to genetic SNP analysis. Blinded genotyping was performed after standard DNA purification and whole genome amplification. In-hospital severe outcomes were defined as either respiratory arrest (RA; defined by mechanical ventilation) or cardiac arrest (CA; defined by loss of pulse). We analyzed 179 patients (61% male, median age 32) who overall suffered 15 RAs and four CAs, of whom three died. The 118G allele conferred 5.3-fold increased odds of CA/RA (p<0.05), while the rs2075572 variant allele was not associated with CA/RA. The 118G variant allele in the OPRM1 gene is associated with worse clinical severity in patients with acute drug overdose. These findings mark the first time that the 118G variant allele is linked with clinical drug overdose vulnerability.

The Toxicology Investigators Consortium Case Registry—The 2012 Experience

Abstract: In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82 % of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or “N-bomb” agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as “synthetic” LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4 % of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.

Case Series: Inhaled Coral Vapor—Toxicity in a Tank

Abstract: Introduction Palytoxin (PTX) is considered a severe marine toxin. Although rare, reports of human exposure from consumption of PTX have described significant morbidity and mortality. PTX is the suspected agent in Haff disease, in which rhabdomyolysis occurs within 24 h of eating contaminated fish such as buffalo fish. PTX is primarily present in soft corals or in dinoflagellates, and it can contaminate crustaceans and other fish as it bioaccumulates up the food chain. Only 23 cases have been reported in the USA, including two recent cases in New York City. Reports of inhalational exposure to PTX are uncommon.

The scientific basis for chelation: animal studies and lead chelation.

Abstract: This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels compared to vehicle-treated controls. A follow-up study in rodents that underwent one or two 21-day courses of succimer treatment showed that chelation significantly reduced brain lead levels, and that two courses of succimer were significantly more efficacious at reducing brain lead levels than one. In both the primate and rodent studies, reductions in blood lead levels were a relatively poor predictor of reductions in brain lead levels. Our studies in rodents demonstrated that it is possible for succimer chelation therapy to alleviate certain types of lead-induced behavioral/cognitive dysfunction, suggesting that if a succimer treatment protocol that produced a substantial reduction of brain lead levels could be identified for humans, a functional benefit might be derived. Finally, we also found that succimer treatment produced lasting adverse neurobehavioral effects when administered to non-lead-exposed rodents, highlighting the potential risks of administering succimer or other metal-chelating agents to children who do not have elevated tissue lead levels. It is of significant concern that this type of therapy has been advocated for treating autism.

Severe anion gap acidosis associated with intravenous sodium thiosulfate administration.

Abstract: Introduction Severe anion gap (AG) acidosis associated with intravenous sodium thiosulfate (STS) administration has not been previously described in nondialysis chronic kidney disease (CKD) patients.

A Case of Sodium Chlorite Toxicity Managed With Concurrent Renal Replacement Therapy and Red Cell Exchange

Abstract: Introduction Sodium chlorite is a powerful oxidizing agent with multiple commercial applications. We report the presentation and management of a single case of human toxicity of sodium chlorite.

In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects.

Abstract: Introduction In the treatment of acetaminophen toxicity, clinicians believe that N-acetylcysteine (NAC) artificially elevates prothrombin time (PT). However, the effect of NAC on human blood coagulation remains unverified. In a previous study, we show that NAC had a dose-dependent effect on PT. To our knowledge, there are no studies that specifically examine the mechanism by which NAC affects PT. This study evaluates the effect from a therapeutic NAC dose on the activity of coagulation factors II, VII, IX, and X in human plasma.