Faculty Bibliography

Although the putative pharmacological targets of synthetic cannabinoids (SCBs) abused in "K2" and "Spice" are similar to Delta(9) -tetrahydrocannabinol (Delta(9) -THC), it remains unclear why SCB toxicity is similar yet different from marijuana. There are obvious potency and efficacy differences, but also important metabolic differences that help explain the unique adverse reactions associated with SCBs. This brief review discusses the limited research on the metabolism of the SCB JWH-018 and contrasts that with the metabolism of Delta(9) -THC.

The Extracorporeal Treatments in Poisoning Workgroup was created to provide evidence-based recommendations on the use of extracorporeal treatments in poisoning. Here, the EXTRIP workgroup presents its recommendations for lithium poisoning. 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. In total, 166 articles met inclusion criteria, which were mostly case reports, yielding a very low quality of evidence for all recommendations. A total of 418 patients were reviewed, 228 of which allowed extraction of patient-level data. The workgroup concluded that lithium is dialyzable (Level of evidence=A) and made the following recommendations: Extracorporeal treatment is recommended in severe lithium poisoning (1D). Extracorporeal treatment is recommended if kidney function is impaired and the [Li(+)] is >4.0 mEq/L, or in the presence of a decreased level of consciousness, seizures, or life-threatening dysrhythmias irrespective of the [Li(+)] (1D). Extracorporeal treatment is suggested if the [Li(+)] is >5.0 mEq/L, significant confusion is present, or the expected time to reduce the [Li(+)] to <1.0 mEq/L is >36 hours (2D). Extracorporeal treatment should be continued until clinical improvement is apparent or [Li(+)] is <1.0 mEq/L (1D). Extracorporeal treatments should be continued for a minimum of 6 hours if the [Li(+)] is not readily measurable (1D). Hemodialysis is the preferred extracorporeal treatment (1D), but continuous RRT is an acceptable alternative (1D). The workgroup supported the use of extracorporeal treatment in severe lithium poisoning. Clinical decisions on when to use extracorporeal treatment should take into account the [Li(+)], kidney function, pattern of lithium toxicity, patient's clinical status, and availability of extracorporeal treatments.

OBJECTIVES: It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. METHODS: This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. RESULTS: There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] = 27.6), bicarbonate < 20 mEq/L (5.4% prevalence, OR = 4.4), and prior cardiac disease (7.1% prevalence, OR = 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value, while presence of two or more risk factors had 90.9% positive predictive value. CONCLUSIONS: The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings.

Background: In the US, deaths from prescription opioids exceed deaths from all illicit drugs combined. Objectives: We aimed to derive risk factors for severe respiratory depression (SRD) and mortality in ED patients with prescription opioid overdose. Methods: This secondary data analysis used data from a prospective cohort of acute drug overdose patients at 2 urban teaching hospitals from 2009-13. We analyzed the subgroup with prescription opioids overdose with these exclusion criteria: age <18, alternate diagnoses, lacking data. The following data was extracted: demographics, initial vital signs, blood gas, ED endotracheal intubation (ETI), naloxone administration, toxicology screen results and in-hospital mortality. The study outcome was SRD defined by either (a) naloxone administration or (b) ETI. Assuming a 20% prevalence of SRD and predictors, we calculated the need to analyze 300 patients to demonstrate 3-fold risk difference with 80% power and 5% alpha. (Table presented) Results: 354 patients were screened, of whom 47 were excluded, leaving 307 patients for analysis (mean age 44.7, 42% females, 2.0% mortality). Prescription opioid overdoses involved the following: oxycodone, 124; methadone, 116; hydrocodone, 31; codeine, 27; morphine, 12; tramadol, 12; buprenorphine, 7; fentanyl, 4; oxymorphone, 3; tapentadol, 2 (some patients exposed to >1). 109 patients met criteria for SRD (90 naloxone alone, 9 ETI alone, 10 both). Mean age was higher in the SRD group (51.1 vs. 41.1, p<0.001), and suicidality was inversely correlated with SRD (OR 0.29, CI 0.17-0.5), while gender had no correlation (p=0.95). Risk for SRD was highly dependent on the type of prescription opioid (see Table 783). In 6 deaths, mortality was associated with tachycardia (p<0.001), hyperlactatemia (p<0.05), and hypotension (p<0.01). Conclusion: In this cohort of patients with prescription opioid overdose, we derived clinical risk factors for SRD (age and specific opioid drugs) as well as mortality (vital sign abnormalities and hyperlactatemia)

Background: Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds developed as probes of the endogenous cannabinoid system or potential therapeutic agents, which clandestine laboratories subsequently synthesize and market as abusable designer drugs. Objectives: We assessed clinical toxicity associated with SCRA overdose, and hypothesized associations with agitation and cardiotoxicity. Methods: This subgroup analysis of a large drug overdose cohort study involved consecutive ED patients at two large urban teaching hospitals collected between 2009-13. Clinical characteristics of patients with exposure to SCRAs (SRCA subgroup) were compared with patients who smoked regular marijuana (MJ 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 (agitation, GCS), and cardiotoxicity (myocardial injury, dysrhythmia). Dysrhythmia was defined as ventricular tachycardia or fibrillation. Assuming 30% prevalence of the predictor and outcome, we calculated the need to enroll 84 patients to show 3.5-fold relative risk with 80% power and 5% alpha. Results: 89 patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 SCRA, 72 MJ, mean age 38.7, 78% males). There were no significant differences between SRCA and MJ with respect to demographics (age, sex, race), exposure history (suicidality, misuse, intent), or vital signs. Laboratory variables associated with SCRA were lower mean bicarbonate (p<0.05) and elevated mean serum glucose (p<0.05). Mental status agitation was significantly more likely in SCRA subgroup (OR 3.3, CI 1.1-9.6). Cardiotoxicity was more pronounced in SCRA subgroup (dysrhythmia OR 9.8, CI 1.0-116). Conclusion: Clinical toxicity of SCRA overdose was much more severe than MJ, including metabolic abnormalities, neurotoxicity and cardiotoxicity. Future studies should assess optimal treatment modalities to prevent adverse clinical outcomes