Dazhe Cao

An Outbreak of Exposure to a Novel Synthetic Cannabinoid

Young men in Colorado presented with altered mental status and seizures after ingestion of a synthetic cannabinoid known as “black mamba.” Medical toxicologists and public health and law enforcement officials identified 263 cases of exposure to this novel substance.

Intravenous lipid emulsion in the emergency department: A systematic review of recent literature

BACKGROUND Intravenous lipid emulsion (ILE) has been broadly attempted in the resuscitation of neurologic and cardiac toxic drug overdoses, however, the role of ILE in the emergency department is poorly defined. OBJECTIVE This review aims to identify recent literature on the use of ILE in humans as an antidote and to familiarize emergency providers with the indications, availability, dosing recommendations, and adverse reactions associated with ILE use. METHODS A systemic literature search of MEDLINE, EMBASE, and major toxicology conference abstracts was performed for human cases using ILE as an antidote with documented clinical outcomes through January 2014. RESULTS Ninety-four published articles and 40 conference abstracts were identified, 85% of which had positive outcomes. The most common indication for ILE was for local anesthetic systemic toxicity (LAST). The most common nonlocal anesthetic xenobiotics were tricyclic-antidepressants and verapamil. DISCUSSION No standard of care is defined for the use of ILE, although the American Heart Association recommends use in LAST, and the American College of Medical Toxicology recommends consideration for circumstances of hemodynamic instability resultant from lipid-soluble xenobiotics. ILE should be administered per American Society of Regional Anesthesia and Pain Medicine dosing recommendations. Laboratory interference, pancreatitis, respiratory distress syndrome, and interference with vasopressors should be considered as risks but are uncommon. CONCLUSIONS In the setting of severe hemodynamic compromise by lipid-soluble xenobiotics, ILE may be considered for resuscitation by emergency physicians. As such, ILE may be stocked in emergency departments in close proximity to resuscitation rooms and areas where local nerve blocks are performed.

Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases

Prostanoid synthesis in mammalian tissues is regulated at the level of prostaglandin H synthase (PGHS) cyclooxygenase catalysis by the availability and structure of substrate fatty acid and the availability of peroxide activator. Two major PGHS isoforms, with distinct pathophysiological functions and catalytic regulation, have been characterized in mammals; a functionally homologous PGHS isoform pair has been cloned from an evolutionarily distant vertebrate, brook trout. The cyclooxygenase activities of recombinant brook trout PGHS‐1 and ‐2 were characterized to test the generality of mammalian regulatory paradigms for substrate specificity, peroxide activation, and product shifting by aspirin. Both trout cyclooxygenases had much more restrictive substrate specificities than their mammalian counterparts, with pronounced discrimination toward arachidonate (20: 4n‐6) and against eicosapentaenoate (20:5n‐3) and do‐cosahexaenoate (22:6n‐3), the latter two prominent in trout tissue lipids. Aspirin treatment did not increase lipoxygenase‐type catalysis by either trout enzyme. Both trout enzymes had higher requirements for peroxide activator than their mammalian counterparts, though the preferential peroxide activation of PGHS‐2 over PGHS‐1 seen in mammals was conserved in the fish enzymes. The divergence in cyclooxygenase characteristics between the trout and mammalian PGHS proteins may reflect accomodations to differences among vertebrates in tissue lipid composition and general redox state.—Liu, W., Cao, D., Oh, S. F., Serhan, C. N., Kulmacz, R. J. Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases. FASEB J. 20, 1097–1108 (2006)

Characterization of edible marijuana product exposures reported to United States poison centers

Abstract Context: Edible marijuana products are sold as brownies, cookies, and candies, which may be indistinguishable from counterparts without marijuana and are palatable to children and adults. The consumption of an entire product containing multiple dose-units may result in overdose. Objective: To characterize edible marijuana exposures reported to US poison centers with subgroup analysis by age. Methods: We analyzed single substance, human exposure calls coded to marijuana brownies, candies, cookies, beverages, or other foods reported to the National Poison Data System from January 2013 to December 2015. Calls were analyzed by state, age, gender, exposure route, clinical effect, therapies, and level of healthcare facility utilization. Results: Four-hundred and thirty calls were reported: Colorado (N = 166, 1.05/100,000 population/year) and Washington (96, 0.46) yielded the highest number of exposures. Three hundred and eighty-one (91%) calls occurred in states with decriminalized medical/recreational marijuana. The number of calls increased every year of the study. The most common age groups were: ≤5 years (N = 109, 0.15/100,000 population/year) and 13–19 (78, 0.09). The most frequent clinical effects were drowsiness/lethargy (N = 118, percentage = 43%), tachycardia (84, 31%), agitated/irritable (37, 14%), and confusion (37, 14%). Children ≤5 years have more drowsiness/lethargy, ataxia, and red eye/conjunctivitis. No deaths were reported. The most common therapies administered were intravenous fluids (85, 20%), dilute/irrigate/wash (48, 11 %), and benzodiazepines (47, 11%). Three patients (ages 4, 10, and 57 years) received intubation. 97 (23%), 217 (50%), and 12 (3%) calls were managed at home, treated/released, admitted to a critical care unit, respectively. Discussion: Although most clinical effects are minor, ventilatory support may be necessary for children and adults. We speculate the increasing exposures may be related to a combination of delayed absorption kinetics of Δ9-tetrahydrocannablnol, lagging packaging regulations, increased accessibility in decriminalized states, and increased familiarity of poison center specialists with edible product codes. Conclusions: Edible marijuana exposures are increasing and may lead to severe respiratory depression.

Perceptions of Basic, Advanced, and Pediatric Life Support Training In a United States Medical School

BACKGROUND Basic Life Support (BLS), Advanced Cardiac Life Support (ACLS), and Pediatric Advanced Life Support (PALS) are integral parts of emergency resuscitative care. Although this training is usually reserved for residents, introducing the training in the medical student curriculum may enhance acquisition and retention of these skills. OBJECTIVES We developed a survey to characterize the perceptions and needs of graduating medical students regarding BLS, ACLS, and PALS training. METHODS This was a study of graduating 4th-year medical students at a U.S. medical school. The students were surveyed prior to participating in an ACLS course in March of their final year. RESULTS Of 152 students, 109 (71.7%) completed the survey; 48.6% of students entered medical school without any prior training and 47.7% started clinics without training; 83.4% of students reported witnessing an average of 3.0 in-hospital cardiac arrests during training (range of 0-20). Overall, students rated their preparedness 2.0 (SD 1.0) for adult resuscitations and 1.7 (SD 0.9) for pediatric resuscitations on a 1-5 Likert scale, with 1 being unprepared. A total of 36.8% of students avoided participating in resuscitations due to lack of training; 98.2%, 91.7%, and 64.2% of students believe that BLS, ACLS, and PALS, respectively, should be included in the medical student curriculum. CONCLUSIONS As per previous studies that have examined this topic, students feel unprepared to respond to cardiac arrests and resuscitations. They feel that training is needed in their curriculum and would possibly enhance perceived comfort levels and willingness to participate in resuscitations.

Cardiac sodium channel blockade after an intentional ingestion of lacosamide, cyclobenzaprine, and levetiracetam: Case report.

Abstract Context. Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose. Case details. A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 μg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10–30 ng/mL), and serum levetiracetam concentration was 22.7 μg/mL (therapeutic: 12–46 μg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae. Discussion. The patients lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation – suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhthmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Point of care testing provides an accurate measurement of creatinine, anion gap, and osmolal gap in ex-vivo whole blood samples with nitromethane.

Abstract Context. Nitromethane interferes with Jaffé measurements of creatinine, potentially mimicking acute kidney injury. Objectives. We determined the proportional contribution of nitromethane in blood samples to creatinine measured by the Jaffé colorimetric and the point-of-care (POC) reactions and determined whether the difference can reliably estimate the concentration of nitromethane. Additionally, we determined whether the presence of nitromethane interferes with anion/osmolal gaps and ascertained the stability of nitromethane in serum after 7 days. Methods. Nitromethane was added to whole blood from four healthy volunteers to achieve concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. The following tests were performed: creatinine (Jaffé and POC), electrolytes (associated with Jaffé and POC), osmolality and nitromethane concentration (gas chromatography [GC]). Remaining samples were refrigerated and reanalyzed using GC at 7 days. Anion and osmolal gaps were calculated. Proportional recovery and degradation of nitromethane were measured using GC. Data were analyzed for agreement with single-factor ANOVA (p = 0.05). Results. Mean creatinine for POC and Jaff methods were 0.93 vs. 0.76 mg/dL, respectively. Jaff creatinine concentrations increased linearly with increasing nitromethane concentrations (R2 = 1, p = 0.01): measured creatinine (mg/dL) = 7.1*nitromethane (mmol/L) = 0.79. POC creatinine remained unchanged across the range of nitromethane concentrations (p = 0.99). Anion and osmolal gaps also remained unchanged. Nitromethane was reliably identified in all sample concentrations using GC on Day 0. Detection of 0.25 mmol/L nitromethane was not consistently recovered on Day 7. Nitromethane degradation was most pronounced at 2 mmol/L concentrations (81% recovery). Conclusions. Nitromethane alters apparent concentration of creatinine using the Jaffé reaction in a linear fashion but not when using the POC reaction. Measured difference between Jaffé and POC creatinine may identify the presence and estimate concentration of nitromethane. Presence of nitromethane did not alter the anion or osmolal gap; thus it would not potentially interfere with the diagnosis of co-exposure to a toxic alcohol.

A little “dab” will do ya’ in: a case report of neuro-and cardiotoxicity following use of cannabis concentrates

Abstract Context: The use of marijuana and cannabis concentrates is increasing, especially following decriminalization in several states. Psychosis and cardiotoxicity have been reported following cannabis use; however, myocardial injury from “dabbing” has not yet been reported. We report a case of hyperthermia, tachycardia, hypertension, severe agitation, neuro-, and cardiotoxicity following the use of “dabs” where there is concomitant confirmatory biological and sample testing. Case details: A 17-year-old athletic man developed agitation requiring sedation and intubation for safety, with peak systolic blood pressures in the 190s and hyperthermia (to 102 °F). He developed elevated serum troponins with persistent tachycardia despite sedation and no clear non-intoxicant etiology. It was discovered that the patient had recently been “dabbing”; an exhaustive search of his home found a sample of the “dabs” which was analyzed along with a comprehensive urine drug screen by tandem liquid mass spectroscopy (t-LCMS) for confirmation. Discussion: Tetrahydrocannabinol (THC) has been increasingly associated with agitation and cardiotoxicity, while cannabidiol (CBD) has been associated with neuroprotective, inhibitory states. We propose that increasing concentrations of THC as well as THC:CBD ratios seen in cannabis concentrates such as “dabs” may cause agitation and end-organ damage through sympathomimetic and serotonergic pathways.

Missed opportunities? An evaluation of potentially preventable poisoning deaths

Abstract Introduction: Although most poisoning deaths are not preventable with current medical technology, in some cases different management decisions may have prevented fatal outcomes. Objective: This study aims to review reported poisoning-related deaths for preventability to provide insight to improve future care. Methods: Fatality abstracts published in the US National Poison Data System (NPDS) Annual Reports (2008–2012) were analyzed. Preventability was graded using a Likert scale of 1 (definitely non-preventable) to 6 (definitely preventable). Two medical toxicologists screened all cases. Cases deemed definitely not preventable (score 1) by both reviewers were excluded from further review and considered to be “non-preventable”. All cases considered at least possibly preventable by either screener were reviewed by a multidisciplinary panel of 5 physicians for preventability scoring. Differences were resolved by consensus. Cases determined to be “preventable” (scores 4–6) were characterized by type of improvement issue involved (diagnosis, treatment, monitoring, other) and recurring scenarios. Results: Of 390 published abstracts, 78 (20.0%) deaths were considered at least possibly preventable by at least one screener. Of these, 34 (8.7%) deaths were determined to be “preventable” by the panel. Inter-observer agreement by weighted kappa analysis was 0.58 for screening, 0.24 for preventability, and 0.44 for specific aspects of care. The most common toxicants were salicylates (n = 9), opioids (n = 4), toxic alcohols (n = 3), fluoride containing product (n = 3), and bupropion (n = 3). The most common improvement opportunities involved treatment and monitoring. Discussion: Most of the ingested substances in preventable deaths have delayed GI absorption or require metabolic activation to produce a delayed effect (such as salicylates, opioids, and toxic alcohols), and therefore provide an opportunity for early recognition and successful interventions. Most improvement opportunities are clearly described in the literature but may be not recognized. Conclusions: Based on an analysis of published NPDS data, a considerable number of poisoning-related deaths reaching medical attention may be preventable. The most common scenarios involved in potentially preventable poisoning fatalities related to monitoring and treatment. Salicylates and opioids were the most common agents involved in preventable deaths.

Hemolytic crisis following acetaminophen overdose in a patient with G6PD deficiency

Sir,While acetaminophen is considered a low-risk analgesic in patients with glucose-6-phosphate dehydrogenase deficiency (G6PDD), case reports of hemolytic anemia following overdose have been publi...