Faculty Bibliography

INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients. METHODS: This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity. RESULTS: Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2-11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0-108). CONCLUSIONS: In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

BACKGROUND: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. METHODS: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. RESULTS: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid(R) 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. CONCLUSION: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have emerged as one tool to combat prescription drug misuse and diversion. New York State mandates that prescribers use its PDMP (called ISTOP) before prescribing controlled substances. We surveyed physicians to assess their experiences with mandatory PDMP use. METHODS: Electronic survey of attending physicians, from multiple clinical specialties, at one large urban academic medical center. RESULTS: Of 207 responding physicians, 89.4% had heard of ISTOP, and of those, 91.1% were registered users. 45.7% of respondents used the system once per week or more. There was significant negative feedback, with 40.4% of respondents describing ISTOP as "rarely" or "never helpful," and 39.4% describing it as "difficult" or "very difficult" to use. Physicians expressed frustration with the login process, the complexity of querying patients, and the lack of integration with electronic medical records. Only 83.1% knew that ISTOP use is mandated in almost all situations. A minority agreed with this mandate (44.2%); surgeons, males, and those who prescribe controlled substances at least once per week had significantly lower rates of agreement (22.6%, 36.2%, and 33.0%, respectively). The most common reasons for disagreement were: time burden, concerns about helpfulness, potential for under-treatment, and erosion of physician autonomy. Emergency physicians, who are largely exempt from the mandate, were the most likely to believe that ISTOP was helpful, yet the least likely to be registered users. 48.4% of non-emergency physicians reported perfect compliance with the mandate; surgeons and males reported significantly lower rates of perfect compliance (18.2% and 36.8%, respectively). CONCLUSIONS: This study offers a unique window into how one academic medical faculty has experienced New York's mandatory PDMP. Many respondents believe that ISTOP is cumbersome and generally unhelpful. Furthermore, many disagree with, and don't comply with, its mandatory use.

Drug overdose is now the leading cause of injury-related mortality in the USA, but the prognostic utility of cardiac biomarkers is unknown. We investigated whether serum cardiac troponin I (cTnI) was associated with overdose mortality. This prospective observational cohort studied adults with suspected acute drug overdose at two university hospital emergency departments (ED) over 3 years. The endpoint was in-hospital mortality, which was used to determine test characteristics of initial/peak cTnI. There were 437 overdoses analyzed, of whom there were 20 (4.6 %) deaths. Mean initial cTnI was significantly associated with mortality (1.2 vs. 0.06 ng/mL, p < 0.001), and the ROC curve revealed excellent cTnI prediction of mortality (AUC 0.87, CI 0.76-0.98). Test characteristics for initial cTnI (90 % specificity, 99 % negative predictive value) were better than peak cTnI (88.2 % specificity, 99.2 % negative predictive value), and initial cTnI was normal in only one death out of the entire cohort (1/437, CI 0.1-1.4 %). Initial cTnI results were highly associated with drug overdose mortality. Future research should focus on high-risk overdose features to optimize strategies for utilization of cTnI as part of the routine ED evaluation for acute drug overdose.

BACKGROUND: Since intentional overdose with rivaroxaban is expected to lead to significant coagulopathy and bleeding, prophylactic reversal has been suggested. We report a single massive ingestion confirmed by a blood concentration that was managed with expectant therapy alone. CASE REPORT: A 71-year-old man with atrial fibrillation, aortic valve replacement, and congestive heart failure presented to the emergency department after an intentional ingestion of 97 (1940 mg total) rivaroxaban tablets in a suicide attempt. Initial laboratories revealed: PT, 60.2 s; INR 7.2; aPTT, 55.7 s; BUN 28 mg/dL; and creatinine 1.2 mg/dL. A whole-blood rivaroxaban concentration obtained on hospital-day three was 160 ng/mL. The patient was admitted for continued observation and the coagulation markers trended downward with no major bleeding events. No reversal agents or blood products were given during his hospitalization. CONCLUSION: In the setting of a single, acute rivaroxaban overdose, with normal renal function, and no active bleeding, conservative therapy alone may be sufficient.

A recent analysis of the American Association of Poison Control Centers database, showed that poisonings from toxins not usually considered amenable to extracorporeal purification ("non-classic toxins" such as ethanol and tricyclic antidepressants) continue to be reported. This publication investigates factors that may explain these findings. Our results suggest that: 1) the relatively high absolute number of ECTR performed for non-classic toxins may simply reflect the large number of exposures to these toxins, 2) poisoning from another toxin may have been the reason for ECTR initiation in some exposures to non-classic toxins, 3) poisoning from non-classic toxins may receive ECTR for purposes other than toxin removal, and 4) the decisional threshold to initiate ECTR may be lower for non-classic toxins because of heightened toxicity.