Lewis S. Nelson

Novel Synthetic Opioids: An Opioid Epidemic Within an Opioid Epidemic

North America is currently facing an opioid epidemic. Opioid overdose deaths have increased 200% since 2000, and in 2014, 28,647 drug-poisoning deaths were attributed to some type of opioid. Multiple sources of opioids contribute to this growing problem and include prescription opioids (including natural and semisynthetic opioids, eg, oxycodone, hydrocodone), methadone, and other synthetic opioids (eg, fentanyl, tramadol); heroin; and other illicit opioids produced in clandestine laboratories. These illicitly produced opioids include nonpharmaceutical fentanyl, fentanyl analogs (eg, acetylfentanyl), and novel synthetic opioids, such as U-47700. The increased incidence of toxicity related to synthetic opioids is highlighted by the case report in this issue by Armenian et al, who describe a case of opioid toxicity related to fentanyl and U-47700 in a patient who believed she was receiving “Norco.” To understand the concerns about nonpharmaceutical fentanyl requires some background about the opioid epidemic. Prescriptions for opioid analgesics paralleled an increase in opioid abuse and fatalities between 2002 and 2010, leveling off from 2011 to 2013. However, drug overdose deaths involving natural and semisynthetic opioids, including the most commonly prescribed opioid pain relievers, oxycodone and hydrocodone, increased by 9% between 2013 and 2014. Increased prescriber education and public awareness of the true harms of opioid overprescribing has likely contributed to improvements in prescribing practices. Additionally, local and regional interventions have led to decreased prescribing and subsequent diversion of prescription opioids. However, as the availability of prescription opioids has decreased, the use and availability of other opioids has increased. This is clearly demonstrated by the significant increase in heroin use in several regions of the United States between 2010 and

The Effect of Opioid Prescribing Guidelines on Prescriptions by Emergency Physicians in Ohio

Study objective The objective of our study is to evaluate the association between Ohio’s April 2012 emergency physician guidelines aimed at reducing inappropriate opioid prescribing and the number and type of opioid prescriptions dispensed by emergency physicians. Methods We used Ohio’s prescription drug monitoring program data from January 1, 2010, to December 31, 2014, and included the 5 most commonly prescribed opioids (hydrocodone, oxycodone, tramadol, codeine, and hydromorphone). The primary outcome was the monthly statewide prescription total of opioids written by emergency physicians in Ohio. We used an interrupted time series analysis to compare pre‐ and postguideline level and trend in number of opioid prescriptions dispensed by emergency physicians per month, number of prescriptions stratified by 5 commonly prescribed opioids, and number of prescriptions for greater than 3 days’ supply of opioids. Results Beginning in January 2010, the number of prescriptions dispensed by all emergency physicians in Ohio decreased by 0.3% per month (95% confidence interval [CI] –0.49% to –0.15%). The implementation of the guidelines in April 2012 was associated with a 12% reduction (95% CI –17.7% to –6.3%) in the level of statewide total prescriptions per month and an additional decline of 0.9% (95% CI –1.1% to –0.7%) in trend relative to the preguideline trend. The estimated effect of the guidelines on total monthly prescriptions greater than a 3‐day supply was an 11.2% reduction in level (95% CI –18.8% to –3.6%) and an additional 0.9% (95% CI –1.3% to –0.5%) decline in trend per month after the guidelines. Guidelines were also associated with a reduction in prescribing for each of the 5 individual opioids, with various effect. Conclusion In Ohio, emergency physician opioid prescribing guidelines were associated with a decrease in the quantity of opioid prescriptions written by emergency physicians. Although introduction of the guidelines occurred in parallel with other opioid‐related interventions, our findings suggest an additional effect of the guidelines on prescribing behavior. Similar guidelines may have the potential to reduce opioid prescribing in other geographic areas and for other specialties as well.

Discerning suicide in drug intoxication deaths: paucity and primacy of suicide notes and psychiatric history

Objective A paucity of corroborative psychological and psychiatric evidence may be inhibiting detection of drug intoxication suicides in the United States. We evaluated the relative importance of suicide notes and psychiatric history in the classification of suicide by drug intoxication versus firearm (gunshot wound) plus hanging/suffocation—the other two major, but overtly violent methods. Methods This observational multilevel (individual/county), multivariable study employed a generalized linear mixed model (GLMM) to analyze pooled suicides and undetermined intent deaths, as possible suicides, among the population aged 15 years and older in the 17 states participating in the National Violent Death Reporting System throughout 2011–2013. The outcome measure was relative odds of suicide versus undetermined classification, adjusted for demographics, precipitating circumstances, and investigation characteristics. Results A suicide note, prior suicide attempt, or affective disorder was documented in less than one-third of suicides and one-quarter of undetermined deaths. The prevalence gaps were larger among drug intoxication cases than gunshot/hanging cases. The latter were more likely than intoxication cases to be classified as suicide versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI, 34.43–49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11–44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11–2.77), or depression (OR, 1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10–1.81). Stratification by mechanism/cause intensified the association between a note and suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06–66.58). Prior suicide attempt (OR, 2.64; 95% CI, 2.19–3.18) and depression (OR, 1.48; 95% CI, 1.17–1.87) were associated with suicide classification in intoxication but not gunshot/hanging cases. Conclusions Without psychological/psychiatric evidence contributing to manner of death classification, suicide by drug intoxication in the US is likely profoundly under-reported. Findings harbor adverse implications for surveillance, etiologic understanding, and prevention of suicides and drug deaths.

Something for pain: Responsible opioid use in emergency medicine

&NA; The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an industry marketing effort that successfully encouraged clinicians to prescribe opioids liberally, and asserted the safety of prescribing opioids for chronic non‐cancer pain, despite a preponderance of evidence demonstrating the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid‐naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction.

Opioid Prescriptions by Specialty in Ohio, 2010–2014

Background The current US opioid epidemic is attributed to the large volume of prescribed opioids. This study analyzed the contribution of different medical specialties to overall opioids by evaluating the pill counts and morphine milligram equivalents (MMEs) of opioid prescriptions, stratified by provider specialty, and determined temporal trends. Methods This was an analysis of the Ohio prescription drug monitoring program database, which captures scheduled medication prescriptions filled in the state as well as prescriber specialty. We extracted prescriptions for pill versions of opioids written in the calendar years 2010 to 2014. The main outcomes were the number of filled prescriptions, pill counts, MMEs, and extended-released opioids written by physicians in each specialty, and annual prescribing trends. Results There were 56,873,719 prescriptions for the studied opioids dispensed, for which 41,959,581 (73.8%) had prescriber specialty type available. Mean number of pills per prescription and MMEs were highest for physical medicine/rehabilitation (PM&R; 91.2 pills, 1,532 mg, N = 1,680,579), anesthesiology/pain (89.3 pills, 1,484 mg, N = 3,261,449), hematology/oncology (88.2 pills, 1,534 mg, N = 516,596), and neurology (84.4 pills, 1,230 mg, N = 573,389). Family medicine (21.8%) and internal medicine (17.6%) wrote the most opioid prescriptions overall. Time trends in the average number of pills and MMEs per prescription also varied depending on specialty. Conclusions The numbers of pills and MMEs per opioid prescription vary markedly by prescriber specialty, as do trends in prescribing characteristics. Pill count and MME values define each specialtys contribution to overall opioid prescribing more accurately than the number of prescriptions alone.

ACMT and AACT position statement: preventing occupational fentanyl and fentanyl analog exposure to emergency responders

To cite this article: Michael J. Moss , Brandon J. Warrick, Lewis S. Nelson, Charles A. McKay, Pierre-André Dubé , Sophie Gosselin , Robert B. Palmer & Andrew I. Stolbach (2017): ACMT and AACT position statement: preventing occupational fentanyl and fentanyl analog exposure to emergency responders, Clinical Toxicology, DOI: 10.1080/15563650.2017.1373782 To link to this article: http://dx.doi.org/10.1080/15563650.2017.1373782

The Role of Clinical Pharmacists in the Emergency Department

Clinical pharmacists are integral to the care and safety of patients in the hospital, particularly in specialty and high-risk settings. Emergency departments (EDs) represent care environments that carry unique risks that may be addressed through the addition of clinical pharmacists specifically trained and/or experienced as an ED pharmacist. Adult and pediatric patients present with undifferentiated medical, neurological, traumatic, psychiatric, and surgical complaints 24 h a day, 7 days a week. Patients are generally unfamiliar to the emergency care providers, may be unable to communicate relevant medical information, and may require time-sensitive interventions. When present, ED crowding is associated with increased risk for medication errors [1–4]. Other factors that raise the risk for error include the expanding pharmacopeia, the increasing complexity of patient drug regimens [5, 6], and problems related to health information technology [7–9]. Despite the evidence supporting the role of pharmacists in the ED and support from national Emergency Medicine groups including the American College of Emergency Physicians [10], some hospitals rely on pharmacy personnel positioned outside the ED. Among EDs with dedicated pharmacists, few have 24-h coverage. This position statement by the American College of Medical Toxicology outlines the importance of dedicated pharmacists in the ED to improve care of adult and pediatric ED patients at all times.

Method overtness, forensic autopsy, and the evidentiary suicide note: A multilevel National Violent Death Reporting System analysis

Objective Higher prevalence of suicide notes could signify more conservatism in accounting and greater proneness to undercounting of suicide by method. We tested two hypotheses: (1) an evidentiary suicide note is more likely to accompany suicides by drug-intoxication and by other poisoning, as less violent and less forensically overt methods, than suicides by firearm and hanging/suffocation; and (2) performance of a forensic autopsy attenuates any observed association between overtness of method and the reported presence of a note. Methods This multilevel (individual/county), multivariable analysis employed a generalized linear mixed model (GLMM). Representing the 17 states participating in the United States National Violent Death Reporting System throughout 2011–2013, the study population comprised registered suicides, aged 15 years and older. Decedents totaled 32,151. The outcome measure was relative odds of an authenticated suicide note. Results An authenticated suicide note was documented in 31% of the suicide cases. Inspection of the full multivariable model showed a suicide note was more likely to manifest among drug intoxication (adjusted odds ratio [OR], 1.70; 95% CI, 1.56, 1.85) and other poisoning suicides (OR, 2.12; 1.85, 2.42) than firearm suicides, the referent. Respective excesses were larger when there was no autopsy or autopsy status was unknown (OR, 1.86; 95% CI, 1.61, 2.14) and (OR, 2.25; 95% CI, 1.86, 2.72) relative to the comparisons with a forensic autopsy (OR, 1.62, 95% CI, 1.45, 1.82 and OR, 2.01; 95% CI, 1.66, 2.43). Hanging/suffocation suicides did not differ from the firearm referent given an autopsy. Conclusions Suicide requires substantial affirmative evidence to establish manner of death, and affirmation of drug intoxication suicides appears to demand an especially high burden of proof. Findings and their implications argue for more stringent investigative standards, better training, and more resources to support comprehensive and accurate case ascertainment, as the foundation for developing evidence-based suicide prevention initiatives.

ACMT and AACT Position Statement: Preventing Occupational Fentanyl and Fentanyl Analog Exposure to Emergency Responders

To cite this article: Michael J. Moss , Brandon J. Warrick, Lewis S. Nelson, Charles A. McKay, Pierre-André Dubé , Sophie Gosselin , Robert B. Palmer & Andrew I. Stolbach (2017): ACMT and AACT position statement: preventing occupational fentanyl and fentanyl analog exposure to emergency responders, Clinical Toxicology, DOI: 10.1080/15563650.2017.1373782 To link to this article: http://dx.doi.org/10.1080/15563650.2017.1373782

ACMT Position Statement: Determining Brain Death in Adults After Drug Overdose

The position of the American College of Medical Toxicology, endorsed by the American Academy of Clinical Toxicology and the Society of Critical Care Medicine, is as follows: We agree with the American Academy of Neurology (AAN) recommendation that the clinical determination of brain death should only be made in the absence of drug intoxication or poisoning. However, a drug screen and clearance calculation using five drug half-lives (T1/2) are not sufficient to exclude intoxication in all cases. Drug screens are not sufficiently comprehensive to detect all drugs that may cause mental status depression. Even when the specific drugs are quantitatively identified, the use of kinetic data to determine clinical effects is limited because drugs often have prolonged half-lives in overdose. For certain drugs and toxins, the duration of effect may extend beyond their detected presence in the vascular space. We recommend identification of drugs or toxins by careful history and targeted testing. An observation period of longer than five half-lives is appropriate when there is a possibility of an extremely large drug overdose, delayed drug absorption, delayed elimination, or interaction with another agent. In cases where brain death is considered but intoxication is unclear, consultation with a medical toxicologist or clinical toxicologist is recommended to guide decisionmaking regarding the timing or appropriateness of clinical testing, as clinical brain death determination cannot take place until intoxication is excluded. While individual practitioners may differ, these are the positions of the ACMT, AACT, and SCCM at the time written, after a review of the issue and scientific literature. The American Academy of Neurology (AAN) offers guidance for the diagnosis of brain death. Brain death is diagnosed clinically when an irreversible and proximate cause of brain injury is identified and no brain function is present upon clinical assessment [1, 2]. A prerequisite of the practice parameters for clinical testing is the absence of Bdrug intoxication or poisoning.^ The only evidence available regarding brain death determination in the setting of intoxication derives from case reports. To determine the extent to which inaccurate brain death determination by clinical testing may occur in this setting, we conducted a review of the literature inMEDLINE and SCOPUS using the search terms Bbrain death mimic^ and Bbrain death drug overdose^ for the dates January 1, 1960 to June 10, 2015. A total of 1394 titles were reviewed for relevance to the topic, and only ten case reports of brain death mimicry were found (three baclofen [3, 4], two snake bites [5, 6], and one each of valproic acid [7], amitriptyline [8], mixed The intent of this position statement is to reduce the likelihood of erroneous declaration of brain death in the setting of drugor toxininduced coma.