Faculty Bibliography

Background: Salicylate (ASA) poisoning remains a significant public health threat with upwards of 20,000 exposures annually in the USA and morbidity/mortality rates of up to 25 %. Identifying predictors of severe outcome allows for targeted treatment to lower these rates. Research Question:What factors are early predictors of severe in-hospital outcomes in ED patients presenting with ASA poisoning? Methods: This was a secondary data analysis of ASA overdoses from a prospective cohort study of suspected acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were enrolled consecutively and were considered eligible for inclusion based on clinical suspicion of ASA ingestion. Children (<18) and alternate diagnoses were excluded. Demographics, clinical parameters, serum ASA concentrations, treatment modalities, and death/admission rate were collected from the medical record. Severe outcome was defined as a composite occurrence of any of the following: acidemia (pH <7.3 or bicarbonate <16 mEq/L), hemodialysis, or death.
Result(s): Forty-eight patients met inclusion criteria, with 43.8 % male, median age 32, mean initial ASA concentration 28.1, and 10 (21 %) classified as severe outcome. There were two deaths, neither of whom received hemodialysis. Patients were treated with sodium bicarbonate in one third of cases, while 54.2 % received activated charcoal and 64.6 % were admitted. Univariate analysis indicated that age (p = 0.04, t test), respiratory rate (RR) (p = 0.04, t test), creatinine (p = 0.05, t test), lactate (p = 0.002, t test), coma (p = 0.05, chi square), and presence of co-ingestions (p = 0.04, chi square) were significantly associated with severe outcome, while ASA alone had no association. However, when adjusted for serum ASA concentration, only age (OR 1.02 per additional year, CI 1.0-1.1), RR (1.09 per additional breath/min, CI 1.03-1.15), creatinine (2.8 per additional mg/dL CI 1.1-7.1), and co-ingestions (OR 6.4, CI 2.3-17.8) were independent predictors of severe outcome.
Discussion(s): We have derived independent predictors of severe outcome from acute ASA poisoning, which can aid in identifying patients who require more aggressive treatment, and does not include serum ASA concentration. Despite the severity of these cases, only one third received sodium bicarbonate, suggesting potential barriers to administration which require further study.
Conclusion(s): Age, RR, creatinine, and co-ingestions are predictive of severe outcome in ED patients with acute ASA poisonin

Endogenous digoxin-like factors (EDLF) are compounds that promote natriuresis, inhibit sodium-potasium-ATPase, and cross-react with antibodies raised against cardiac glycosides. Although EDLF are well described in experimental animal models and a variety of clinical conditions in humans, no investigation previously evaluated an association between EDLF and hypothermia. We used two separate models to examine the presence of EDLF in hypothermic humans. The first study consisted of a case-controlled comparison of patients with unintentional environmental hypothermia. All patients with environmental hypothermia were prospectively enrolled if they were not taking cardiac glycosides and had no conditions previously associated with EDLF. A digoxin concentration obtained at presentation was compared to one obtained from presentation on patients from a demographically matched control group of normothermic patients. The second study enrolled a convenience sample of patients undergoing controlled cold cardioplegia for surgery. Once again, patients were excluded for conditions previously associated with EDLF, and were required to have a non-detectable preoperative digoxin concentration. Digoxin concentrations were subsequently compared in the pre- and post-operative periods. In addition to serving as their own controls, a comparison group of normothermic patients were added to help control for confounding factors associated with surgery under general anesthesia. Twenty-two patients with environmental hypothermia (mean temperature 91° Fahrenheit, range, 83.8-93.8° Fahrenheit) and 22 controls were included in the first study. Ten hypothermic patients had measurable digoxin concentrations, 6 of which were above 0.15 ng/mL. All control patients had digoxin concentrations of 0.00 ng/mL (p = 0.03, Fisher's exact test). The second study enrolled ten patients undergoing surgery with cold cardioplegia and ten control patients undergoing normothermic surgery under general anesthesia. None of the ten control patients had measurable digoxin concentrations on either pre or postoperative testing. Although all of the cold cardioplegia hypothermic patients had negative preoperative digoxin concentrations, one developed a postoperative concentration of 0.44 ng/mL. We conclude that hypothermia is associated with the presence of EDLF. An animal model and further human testing will be required to establish causation

BACKGROUND: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup was formed to provide recommendations on the use of extracorporeal treatments (ECTR) in poisoning. Here, we present our results for digoxin. METHODS: After a systematic literature search, clinical and toxicokinetic data were extracted and summarized following a predetermined format. The entire workgroup voted through a two-round modified Delphi method to reach a consensus on voting statements. A RAND/UCLA Appropriateness Method was used to quantify disagreement, and anonymous votes were compiled and discussed in person. A second vote was conducted to determine the final workgroup recommendations. RESULTS: Out of 435 articles screened, 77 met inclusion criteria. Only in-vitro, animal studies, case reports and case series were identified yielding a very low quality of evidence for all recommendations. Based on data from 84 patients, including six fatalities, it was concluded that digoxin is slightly dialyzable (level of evidence = B), and that ECTR is unlikely to improve the outcome of digoxin-toxic patients whether or not digoxin immune Fab (Fab) is administered. Despite the lack of robust clinical evidence, the workgroup recommended against the use of ECTR in cases of severe digoxin poisoning when Fab was available (1D) and also suggested against the use of ECTR when Fab was unavailable (2D). CONCLUSION: ECTR, in any form, is not indicated for either suspected or proven digoxin toxicity, regardless of the clinical context, and is not indicated for removal of digoxin-Fab complex.

BACKGROUND: Novel psychoactive substances (NPS) are emerging at an unprecedented rate. Likewise, prevalence of use and poisonings has increased in recent years. OBJECTIVE: To compare characteristics of NPS exposures and non-NPS-drug-related exposures and to examine whether there are differences between exposures involving synthetic cannabinoid receptor agonists (SCRAs) and other NPS. METHODS: Poison control center data from the five counties of New York City and Long Island were examined from 2011-2014. We examined prevalence and characteristics of NPS exposures (classified as intentional abuse) and compared characteristics of cases involving SCRAs and other NPS. RESULTS: Prevalence of NPS exposures was 7.1% in 2011, rising to 12.6% in 2014. Most exposures (82.3%) involved SCRA use. The second and third most prevalent classes were phenethylamines/synthetic cathinones ("bath salts"; 10.2%) and psychedelic phenethylamines (4.3%). Compared to other drug-related exposures (i.e. involving licit and illicit drugs), those who used NPS were more likely to be younger, male, and to have not co-used other drugs (ps < 0.001). SCRA exposures increased sharply in 2014 and the mean age of users increased over time (p < 0.01). Females exposed to SCRAs were younger than males (p < 0.001), and in 2014, individuals exposed to SCRAs were more likely to report concomitant use of alcohol than users of other NPS (p = 0.010). Users of other NPS were more likely than SCRA users to report concomitant use of ecstasy/3,4-methylenedioxymethamphetamine (MDMA)/"Molly" (p < 0.001). CONCLUSION: Exposures reported to the poison center that involve NPS are increasing and the majority involve SCRAs. These findings should inform prevention and harm reduction approaches.

Context Although the clinical use of intravenous lipid emulsion therapy for the treatment of lipophilic drug toxicity is increasing, the focus of most publications is on outcome in laboratory animals or in patients. An unintended consequence of intravenous lipid emulsion is the creation of extremely lipemic blood, which may interfere with the laboratory analysis or interpretation of common analytes. Objective The American Academy of Clinical Toxicology has established a lipid emulsion workgroup to review the evidence and produce recommendations on the use of this novel therapy for drug toxicity. The aim of this subgroup is to review the available evidence regarding the effect of intravenous lipid emulsion on common laboratory testing, which often forms the basis of the appraisal of the balance between benefits and potential adverse events. Methods We performed a comprehensive review of the literature. Relevant articles were determined based upon a predefined methodology. Package inserts of manufacturers' assays were collected. Article inclusion required that the article met predefined inclusion criteria with the agreement of at least two members of the subgroup. Results We included thirty-six articles in the final analysis. Evaluation of the reviewed analytes revealed heterogeneity with regards to the assessment of the effect of intravenous lipid emulsion in terms of consistency and magnitude of effect across the different analytic platforms. Conclusions The measurements of a number of common analytes can be markedly affected by the lipemia produced by lipid emulsions such that they cannot always be interpreted in the way that most physicians use this information in typical clinical situations. In fact, a lack of appreciation of this effect may lead to unintentional treatment errors. Because the effect of the lipemia produced is dependent on the reagents and laboratory platform used, it would be useful for all future reports to clearly document sample handling, reagents and laboratory platform used, as well as any procedures employed to reduce the lipid content.

CONTEXT: Solanum torvum berries, known as susumber or turkey berries, are prepared as part of traditional Jamaican dishes usually served with cod and rice. Poisoning is rare. Although toxic compounds have never been definitively isolated, previous reports suggest toxicity results from inhibition of acetylcholinesterases. We present a case of susumber berry poisoning with detailed electromyographic studies and laboratory analysis. CASE DETAILS: A 54-year-old woman presented to the Emergency Department (ED) complaining of vision, speech, and gait changes; emesis; and diffuse myalgias following consumption of susumber berries. The physical examination demonstrated an intact, lucid mental status, miosis, opsoclonus, severe dysarthria, dysmetria, mild extremity tenderness and weakness, and inability to ambulate. Her symptom constellation was interpreted as a stroke. DISCUSSION: Electromyography demonstrated a pattern of early full recruitment as well as myotonia during the period of acute toxicity. Additionally, solanaceous compounds, in particular solasonine and solanidine, were identified in leftover berries and the patient's serum. Store-bought commercial berries and subsequent serum samples were free of such toxic compounds. EMG studies, together with a laboratory analysis of berries or serum can assist in the differential diagnosis of stroke, and provide both a prognostic screening and confirmation of suspected glycoside toxicity.