IntroductionUse of synthetic cannabinoids (SC) has recently emerged as a new drug epidemic. Our emergency departments (EDs) received a surge of SC users presenting with lethargy and bradycardia, contrasting prior reports of SC-induced tachycardia and agitation. Our goal was to describe these novel presentations and characterize the compounds.MethodsWe present a case series of patients with SC intoxication who presented to our toxicology service covering two tertiary care EDs between 2/11/2015 and 6/23/2015. A retrospective chart review recorded initial vital signs, chief complaint and clinical course. Urine, blood and xenobiotic samples were analyzed using either liquid chromatography/mass spectrometry or gas chromatography/mass spectrometry. We compared resulting spectra against databases containing numerous SCs or metabolites and scored based on a reference comparison.ResultsBetween 2/11/2015 and 6/23/2015, we identified 141 visits. Males comprised 139 visits (age range 21–68 years; median 35, interquartile range 20). Sixty-eight percent presented with lethargy or loss of consciousness. Hypotension (SBP <90 mmHg) and bradycardia (HR<60 bpm) were seen in 10% and 24% of visits, respectively. While most patients were discharged after observation, three were admitted to the intensive care unit and seven to telemetry. Admissions were for vital sign instability, bradycardia requiring pacing, prolonged sedation and respiratory failure requiring mechanical ventilation.Laboratory analysis revealed SC in the XLR-11 family in 18/36 drug, 9/12 blood, and 23/31 urine samples. Carboxamide indazole derivative (CID) family compounds were detected in 13/36 drug samples, 21/31 urine samples, but no blood samples; 11/31 drug samples contained both XLR-11 and CID. Other compounds detected included PB-22 and nicotine. No JWH compounds, opiates, imidazoline receptor agonists, benzodiazepines or other sedative-hypnotics were detected.ConclusionUnlike their predecessors, novel SC may be associated with significant central nervous system depression and bradycardia. While prior reports indicated that SC mostly contained JWH compounds, none were detected in these samples. The most commonly identified compounds in this series were CID and alkyl SC derivatives, such as INACA compounds and XLR-11. These tend to be full agonists at the cannabinoid receptor and are presumably more potent. The lack of other depressants suggests that the clinical findings are due to the combination of these compounds and not coingestants or adulterants. SC intoxication should be considered for patients with undifferentiated psychomotor depression and bradycardia.

This case report highlights the challenges associated with the diagnosis and workplace evaluation of occupationally acquired ultraviolet (UV) radiation-induced photokeratitis and associated skin burns in a group of restaurant workers. UV-C spectrum bulbs were inadvertently shipped and installed in insect light traps. Ocular and dermal symptoms were reported in 18 of 85 restaurant employees to varying degrees of severity over a 2-day period. One patient was formally diagnosed with a chemical burn/irritation of the cornea. More severe symptoms were reported by individuals working in close proximity to the lights. This clinical picture can resemble mass chemical or irritant exposure when multiple individuals are affected, and a multidisciplinary approach was required for rapid identification of the source to limit morbidity. Prevention strategies for similar events should be considered which can include limiting hardware compatibility and improving warning labels.

Article: Schiele F, van Ryn J, Newsome C, et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121: 3554-3562.Keywords: Dabigatran, Fab antidote, Preclinical research. Background: Advances in anticoagulation for patients at risk for thromboembolic disorders have led from the use of indirect thrombin inhibitors (like warfarin) to direct inhibitors including dabigatran. Dabigatran therapy is more convenient for patients and has less reported complications than warfarin in large studies. However, when bleeding occurs during dabigatran therapy or a need for emergent surgery arises, there is no effective reversal modality and mortality in these circumstances is seemingly high.Research objective: Characterize the structure and test the ability of a novel anti-dabigatran fab to reverse anticoagulant effects x and in vivo.Methods: Antibodies were cloned after dabigatran exposure in mice, purified, and then humanized. The antidabigatran fab was then tested in vitro for the ability to reverse dabigatran anticoagulation, structurally characterized via crystallography, and examined for intrinsic coagulant effect. The derived fab was also tested in vivo in dabigatrananticoagulated rats.Results: Intact mouse antibodies, purified mouse antibodies, and humanized fab bound dabigatran as measured via ELISA. These antibodies also reversed prolonged plasma thrombin time in a dose dependent manner. Detailed crystallography revealed that the final humanized fab is composed of two variable light and heavy chain domains and two constant domains. The dabigatran binding site is a polar pocket surrounded by a hydrophobic area. Dabigatran binds at the polar pocket in a similar manner to thrombin binding. In the third phase of the study, investigators performed further assays to investigate fab binding to thrombin and other thrombin substrates. There was no observed binding nor procoagulant effects. Lastly, a single fab dose reversed prolonged thrombin time in rats despite continuous infusion of dabigatran.Conclusion: The derived anti-dabigatran fab bound with high affinity, reversed anti-coagulant effects in vitro/in vivo, and lacked intrinsic thrombin-like procoagulant effects.Critique: This is an elegant study that demonstrates the ability to produce a novel fab that specifically binds to dabigatran and reverses its anticoagulant effect without untoward procoagulant activity. All investigators are employees of the manufacturer of dabigatran.Implication for toxicologists: This report is promising in that we may have an effective and safe therapy for direct thrombin inhibitor in the reasonable future.Article: Manini AF, Stimmel B, Vlahov D. Racial susceptibility for QT prolongation in acute drug overdose. J Electrocardiol. 2014 (in press).