A cross-sectional analysis of fentanyl analog exposures among living patients.

Background: Synthetic opioids, including fentanyl analogs, contribute to an increasing proportion of opioid-related deaths. Highly potent analogs pose an increased risk for fatal overdose. The prevalence of fentanyl analog exposures in patients with known opioid exposure is unknown.Objective: The purpose of this study was to determine the exposure prevalence for fentanyl analogs in living patients with positive urine screens for opiates or fentanyl.Methods: This was a cross-sectional analysis of urine high performance liquid chromatography/tandem mass spectroscopy (HPLC-MS/MS) results from patients with a positive urine screen for opiates or fentanyl at a large public healthcare system in Chicago, Illinois. Samples with positive screens were non-continuously tested by HPLC-MS/MS for 5 selected months in 2018 and 2019.Results: A total of 219 urine samples which screened positive for fentanyl or opiates underwent HPLC-MS/MS testing. At least one fentanyl analog was detected in 65.3% (n = 143) of samples with 26.0% (n = 57) testing positive for multiple analogs. The most common analogs, intermediates, or metabolites were: 4-ANPP (n = 131); 2-furanylfentanyl (n = 22); acryl fentanyl (n = 21); butyrylfentanyl (n = 15); cyclopropylfentanyl (n = 15); and carfentanil (n = 13). Of samples which screened positive for fentanyl (n = 188), 70.2% (132) tested positive for at least one fentanyl analog. Of samples which screened negative for fentanyl but positive for opiates (n = 31), 35.5% (n = 11) tested positive for fentanyl analogsConclusion: Fentanyl analog exposure is common in patients with positive urine screens for fentanyl or opiates. Screening living patient samples for synthetic opioids has future toxicosurveillance implications and these data underscore the increased risks from illicit opioid use.

Take-Home Naloxone Program Implementation: Lessons Learned From Seven Chicago-Area Hospitals.

Despite consensus recommendations from the American College of Emergency Physicians (ACEP), the Centers for Disease Control and Prevention, and the surgeon general to dispense naloxone to discharged ED patients at risk for opioid overdose, there remain numerous logistic, financial, and administrative barriers to implementing "take-home naloxone" programs at individual hospitals. This article describes the recent collective experience of 7 Chicago-area hospitals in implementing take-home naloxone programs. We highlight key barriers, such as hesitancy from hospital administrators, lack of familiarity with relevant rules and regulations in regard to medication dispensing, and inability to secure a supply of naloxone for dispensing. We also highlight common facilitators of success, such as early identification of a "C-suite" champion and the formation of a multidisciplinary team of program leaders. Finally, we provide recommendations that will assist emergency departments planning to implement their own take-home naloxone programs and will inform policymakers of specific needs that may facilitate dissemination of naloxone to the public.

Treatment of acute naloxone-precipitated opioid withdrawal with buprenorphine.

Naloxone is a frequently utilized and effective treatment to reverse the life-threatening effects of illicit opioid intoxication. Excessive naloxone dosing in these circumstances, however, may lead to naloxone-precipitated opioid withdrawal in individuals with opioid dependence. Buprenorphine, a partial mu-opioid agonist, is increasingly utilized in the Emergency Department (ED) for the treatment of opioid withdrawal syndrome but little is known regarding its utility in cases of naloxone-precipitated opioid withdrawal. We report a case of naloxone-precipitated opioid withdrawal that was effectively treated with sublingual buprenorphine. An older male was brought into the ED with signs and symptoms of opioid toxicity that was successfully treated with pre-hospital naloxone by Emergency Medical Services. He had a clinical opioid withdrawal scale (COWS) or 10 with abdominal cramping and unintentional defecation. After a discussion of treatment options and possible adverse effects with the patient, the decision was made to administer 4 mg/1 mg of sublingual buprenorphine/naloxone film. The patient reported a rapid improvement in symptoms and at 30 min posttreatment, his COWS was 4. His COWS decreased to 3 at 1 h and this was sustained for 4 h of observation. The patient was subsequently discharged to a treatment facility for opioid use disorder. This case highlights the potential of buprenorphine as a treatment modality for acute naloxone-precipitated opioid withdrawal. Due to the risks of worsening or sustained buprenorphine-precipitated opioid withdrawal, further research is warranted to identify patients who may benefit from this therapy.

Health Care Utilization of Opioid Overdose Decedents with No Opioid Analgesic Prescription History.

Opioid overprescribing is a major driver of the current opioid overdose epidemic. However, annual opioid prescribing in the USA dropped from 782 to 640 morphine milligram equivalents per capita between 2010 and 2015, while opioid overdose deaths increased by 63%. To better understand the role of prescription opioids and health care utilization prior to opioid-related overdose, we analyzed the death records of decedents who died of an opioid overdose in Illinois in 2016 and linked to any existing controlled substance monitoring program (CSMP) and emergency department (ED) or hospital discharge records. We found that of the 1893 opioid-related overdoses, 573 (30.2%) decedents had not filled an opioid analgesic prescription within the 6 years prior to death. Decedents without an opioid prescription were more likely to be black (33.3% vs 20.2%, p < .001), Hispanic (16.3% vs 8.8%, p < .001), and Chicago residents (46.8% vs 25.6%, p < .001) than decedents with at least one filled opioid prescription. Decedents who did not fill an opioid prescription were less likely to die of an overdose involving prescribed opioids (7.3% vs 19.5%, p < .001) and more likely to fatally overdose on heroin (63% vs 50.4%, p < .001) or fentanyl/fentanyl analogues (50.3% vs 41.8%, p = .001). Between 2012 and the time of death, decedents without an opioid prescription had fewer emergency department admissions (2.5 ± 4.2 vs 10.6 ± 15.8, p < .001), were less likely to receive an opioid use disorder diagnosis (41.3% vs 47.5%, p = .052), and were less likely to be prescribed buprenorphine for opioid use disorder treatment (3.3% vs 8.6%, p < .001). Public health interventions have often focused on opioid prescribing and the use of CSMPs as the core preventive measures to address the opioid crisis. We identified a subset of individuals in Illinois who may not be impacted by such interventions. Additional research is needed to understand what strategies may be successful among high-risk populations that have limited opioid analgesic prescription history and low health care utilization.

Comparison of High-Fidelity Medical Simulation to Short-Answer Written Examination in the Assessment of Emergency Medicine Residents in Medical Toxicology.

We compared high-fidelity medical simulation to short-answer written examination in the assessment of emergency medicine residents (EMR) on a month-long medical toxicology rotation. Knowledge-based assessment tools using cases of an aspirin overdose and a tricyclic antidepressant overdose were used to assess all consecutive rotating EMR (n=53). Assessment by simulation had similar accuracy and precision but higher satisfaction rates when compared to written examination. Incorporating simulation into the ABEM certifying examination warrants further study.

Digoxin-Specific Antibody Fragment Dosing: A Case Series.

Digoxin-specific antibody fragments (DSFab) are used for the treatment of poisoning by cardiac glycosides, such as pharmaceutical digoxin. Dosing of this therapy for chronic and acute poisonings is based on the steady-state serum concentrations of digoxin, historical data in acute ingestions, or empiric regimens purportedly based on the average requirements. Empiric dosing for adult patients involves utilization of 3-6 vials for chronic poisoning and 10-20 vials for acute poisoning. The aim of this study was to describe the average dosing requirements based on the steady-state serum concentration of digoxin or historical data and compare this with the empiric dosing regimens. We performed a retrospective analysis of cases over an 11-year period presented to the Illinois Poison Center where administration of DSFab was recommended. We identified 140 cases of chronic digoxin poisoning and 26 cases or acute digoxin poisoning for analysis. The average dose of DSFab recommended in the cases of chronic digoxin poisoning was 3.05 vials (SD ± 1.31). The average dose of DSFab recommended in the cases of acute digoxin poisoning was 6.33 vials (SD ± 5.26). These values suggest that empiric dosing regimens may overestimate the need for DSFab in cases of both chronic and acute poisonings of pharmaceutical digoxin.

The effect of prehospital nebulized naloxone on suspected heroin-induced bronchospasm.

BACKGROUND: Snorting or smoking heroin is a known trigger of acute asthma exacerbation. Heroin abuse may be a risk factor for more severe asthma exacerbations and intubation. Heroin and other opioids provoke pulmonary bronchoconstriction. Naloxone may play a role in decreasing opioid-induced bronchospasm. There are no known clinical cases describing the effect of naloxone on opioid-induced bronchospasm. METHODS: This is an observational study in which nebulized naloxone was administered to patients with suspected heroin-induced bronchospasm. Patients with spontaneous respirations were administered 2 mg of naloxone with 3 mL of normal saline by nebulization. We describe a case series of administrations for suspected heroin-induced bronchospasm. RESULTS: We reviewed 21 administrations of nebulized naloxone to patients with suspected heroin-induced bronchospasm. Of these, 19 patients had a clinical response to treatment documented. Thirteen patients displayed clinical improvement (68%), 4 patients had no improvement (21%), and 2 patients worsened (10%). Of the 2 patients who had clinical decline, none required intubation. Of the patients who improved, 1 patient received only nebulized naloxone and 1 patient received naloxone and albuterol together. Seven patients showed clinical improvement after the administration of albuterol, atrovent, and naloxone together as a combination. Four patients showed additional improvement when the naloxone was administered after the albuterol and atrovent combination. CONCLUSION: Naloxone may play a role in reducing acute opioid-induced bronchoconstriction, either alone or in combination with albuterol. Future controlled studies should be conducted to determine if the addition of naloxone to standard treatment improves bronchospasm without causing adverse effects.

Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose?

BACKGROUND: Emergency medical services (EMS) traditionally administer naloxone using a needle. Needleless naloxone may be easier when intravenous (IV) access is difficult and may decrease occupational blood-borne exposure in this high-risk population. Several studies have examined intranasal naloxone, but nebulized naloxone as an alternative needleless route has not been examined in the prehospital setting. OBJECTIVE: We sought to determine whether nebulized naloxone can be used safely and effectively by prehospital providers for patients with suspected opioid overdose. METHODS: We performed a retrospective analysis of all consecutive cases administered nebulized naloxone from January 1 to June 30, 2010, by the Chicago Fire Department. All clinical data were entered in real time into a structured EMS database and data abstraction was performed in a systematic manner. Included were cases of suspected opioid overdose, altered mental status, and respiratory depression; excluded were cases where nebulized naloxone was given for opioid-triggered asthma and cases with incomplete outcome data. The primary outcome was patient response to nebulized naloxone. Secondary outcomes included need for rescue naloxone (IV or intramuscular), need for assisted ventilation, and adverse antidote events. Kappa interrater reliability was calculated and study data were analyzed using descriptive statistics. RESULTS: Out of 129 cases, 105 met the inclusion criteria. Of these, 23 (22%) had complete response, 62 (59%) had partial response, and 20 (19%) had no response. Eleven cases (10%) received rescue naloxone, no case required assisted ventilation, and no adverse events occurred. The kappa score was 0.993. CONCLUSION: Nebulized naloxone is a safe and effective needleless alternative for prehospital treatment of suspected opioid overdose in patients with spontaneous respirations.

Take-Home Naloxone and the Need for a Publicly Funded Naloxone Supply.

The opioid crisis continues to exact a heavy toll on the United States, and overdose deaths have only increased during the current global pandemic. One effective intervention to reduce overdose deaths is to distribute the opioid antagonist naloxone directly to persons actively using opioids (ie, "take-home naloxone"), especially at touchpoints with the potential for significant impact such as emergency departments and jails. A number of hospital emergency departments have recently sought to implement individual take-home naloxone programs; however, programmatic success has been inconsistent due primarily to the inability to secure reliable funding for a naloxone supply. In this commentary, we establish the argument for a publicly funded naloxone supply to support take-home naloxone distribution in emergency department settings. We posit that the complex billing and reimbursement system for medication dispensing is impossibly burdensome during emergency care for an acute opioid overdose, and that the mounting death toll from this public health crisis demands a strong commitment to harm reduction. A publicly financed naloxone supply would demonstrate this commitment and make a measurable impact in saving lives. Ultimately, provision of naloxone should be coupled with other comprehensive treatment services and medications for opioid use disorder to meaningfully reduce harms associated with opioid use.

Applying Project ECHO (Extension for Community Health Care Outcomes) to improve addiction care in rural emergency departments.

Background: Advancements in research and legislation have improved emergency provider ability to treat opioid use disorder (OUD), but dissemination into rural emergency departments (EDs) is limited. Project Extension for Community Healthcare Outcomes (ECHO) allows community generalists to learn from specialists through telementoring. We aimed to use ECHO to facilitate knowledge translation, increase confidence, and change behavior of rural ED providers treating patients with OUD. Methods: Stakeholder interviews were conducted with rural ED providers. A group of ED addiction experts created an ECHO curriculum with eight OUD topics. ED health professionals were recruited and completed pre/post surveys centered around knowledge and comfort with treating OUD in the ED, with focus on clinical practice and stigma. Following the ECHO model, sessions included a 20-min didactic followed by two cases presented by participants, with discussion facilitated by faculty. Results: Twenty-seven participants registered; seven attended ≥75% of sessions and completed both surveys. Of the seven, three were physicians, two advanced practice providers, one nurse, and one clinical pharmacist. Eight 1-hour sessions were conducted in two cohorts between January and December 2021. On a 5-point Likert scale, respondents on average agreed with questions evaluating acceptability (mean ± SD 3.96 ± 0.64), appropriateness (mean ± SD 4.18 ± 1.18), and feasibility (mean ± SD 4.00 ± 1.17). Participants had a 1.09-point increase (paired t-test = 2.43, p = 0.05) on 7-point Likert-scale questions measuring self-efficacy and a 0.13-point change (paired t-test = 2.64, p = 0.04) on 4-point Likert scale questions measuring stigmatizing attitudes (reduction of attitudes). A total of 71% (5/7) reported changes in clinical practice and 57% (4/7) in departmental protocols after participation. Conclusions: Our ED OUD ECHO course successfully created a model for rural ED providers to learn from ED addiction experts. It was well received and impacted self-reported provider stigmatizing attitudes, patient-facing behavior, and departmental initiatives. Recruitment was challenging and participation was limited. Future efforts will target maximizing recruitment.

Effect of cyclodextrin infusion in a rat model of verapamil toxicity.

Sulfobutylether-ß-cyclodextrin (SBE-CD) is a pharmaceutical excipient known to bind verapamil. After intravenous administration, clearance of SBE-CD approximates glomerular filtration rate. We hypothesized that SBE-CD would complex with verapamil in vivo, enhance renal elimination, and increase time to death in a rat model of verapamil toxicity. Ten Wistar rats were allocated to control or intervention groups. All received isoflurane anesthesia followed by verapamil infusion (32 mg/kg) over 1 hour. The control group received saline bolus 7.5 mL/kg at 5 minutes. The intervention group received SBE-CD infusion 7.5 mL/kg (2.25 g/kg) at 5 minutes. Heart rate, respiratory rate, oxygen saturation, and temperature were monitored. The primary endpoint was time to death measured separately as time to asystole and time to apnea. There was no benefit derived from cyclodextrin infusion. Average time to death was significantly longer in the control group as measured by time to apnea (P < 0.05). Control group survival was significantly better as measured by time to asystole and time to apnea (Breslow P < 0.05). SBE-CD infusion resulted in a shorter time to death measured by time to apnea and asystole. Preliminary work demonstrated no effect in isoflurane anesthetized rats receiving only SBE-CD bolus. Verapamil poisoned rats treated with 2.25 g/kg of SBE-CD showed increased toxicity. We propose that this effect was related to the large hyperosmolar CD infusion combined with verapamil-induced cardiogenic shock. Additional studies are warranted to clarify the mechanism of increased toxicity in our study and to assess for potential beneficial effects at lower SBE-CD concentrations.

Whole bowel irrigation and the hemodynamically unstable calcium channel blocker overdose: primum non nocere.

Sustained-release calcium channel blocker (CCB SR) overdoses are potentially life-threatening ingestions. These patients may not become hemodynamically unstable until many hours after ingestion. On theoretical grounds, some have suggested that whole bowel irrigation (WBI) with polyethylene glycol electrolyte lavage solution may be of value in the management of these cases. We report two cases with poor outcome (including one fatality) that were complicated by the use of WBI. Both cases were treated with WBI beginning before and continuing after developing hypotension. WBI should be avoided in the setting of the hemodynamically unstable CCB SR overdose.

An outbreak of severe coagulopathy from synthetic cannabinoids tainted with Long-Acting anticoagulant rodenticides.

Objective: To describe a large regional poison center's experience managing an outbreak of long-acting anticoagulant rodenticide (LAAR) poisoning associated with synthetic cannabinoid (SC) use.Methods: This is a retrospective review of exposures reported to the Illinois Poison Center between March 10 and August 1, 2018. All cases coded as exposure to Δ9-tetrahydrocannabinol homologs were identified. Patients with suspected SC use, positive LAAR testing, and coagulopathy (signs or symptoms of bleeding or international normalized ratio [INR] > 2) were included. If confirmatory LAAR testing was performed and resulted as negative, the patient was excluded from this analysis. In the absence of LAAR testing, patients with suspected SC use, an INR >2, and no alternative explanation of coagulopathy were included. Suspected SC use was defined as use suspected by a member of the treating team or reported by the patient. Presenting signs and symptoms, laboratory findings, management, healthcare utilization, outcomes, and disposition of patients affected by this outbreak were reported.Results: One hundred seventy-eight cases met inclusion criteria. Most patients were male (73%) and young to middle-aged (median age 32, IQR 25-40). Most presented to hospitals in Peoria (35%) and Cook (31%) counties. Median hospitalization was three days (IQR 2-4). Eighty-eight percent of patients presented with an INR >10. Eighteen cases had qualitative anticoagulant testing, all of which were positive for brodifacoum. Other identified LAARs included difenacoum (10/18) and bromadiolone (1/18). Sixty-three percent of patients had back, flank or abdominal pain; 70% of patients presented with hematuria. One hundred six cases received IV vitamin K1; no adverse or anaphylactoid reactions were reported. Forty-one (22%) patients left AMA. Thirty-eight patients (21%) were re-hospitalized during the study period. Patients leaving AMA were 1.6 times more likely to be re-hospitalized than patients with other dispositions. Intracranial hemorrhage, present in 3% of total cases, was present in 4 of 5 fatalities.Conclusions: We describe an outbreak of multiple LAARs contaminating SCs. Patients presented with bleeding from varied sites, often required blood products, factor replacement, and high dose vitamin K1 for stabilization.

Bupropion-associated QRS prolongation unresponsive to sodium bicarbonate therapy.

We describe a case of bupropion-associated QRS prolongation that was unresponsive to intravenous bolus therapy of sodium bicarbonate. Bupropion may cause seizures and conduction delays similar to tricyclic antidepressants in the overdose setting by an unknown mechanism.

Parenteral ophthalmic tropicamide or cyclopentolate protects rats from lethal organophosphate poisoning.

We determine the efficacy of parenteral ophthalmic antimuscarinic agents (tropicamide ophthalmic 1% and cyclopentolate hydrochloride ophthalmic 1%) on survivability in a rat model of acute, lethal organophosphate pesticide (OP) poisoning. After obtaining an appropriate dose-response for study comparison, rodents were randomized to receive 1 of 4 intraperitoneal antidotes; (1) 0.3 mL normal saline, (2) atropine 10 mg/kg, (3) ophthalmic tropicamide 20 mg/kg, or (4) ophthalmic cyclopentolate 20 mg/kg. Five minutes after pretreatment, 15 mg/kg of dichlorvos was administered subcutaneously. Mortality rates and time to death were compared using Fisher exact test and the Kaplan-Meier method with log-rank test, respectively. If alive at 120 minutes, survival was assumed and the study was terminated. Survival in rats pretreated with atropine (10 mg/kg) was 90%. Survival in rats pretreated with tropicamide (20 mg/kg) and cyclopentolate (20 mg/kg) were 90% [P < 0.01; 95% confidence interval (CI) 0.71-1.09] and 90% (P < 0.01; 95% CI 0.71-1.09), respectively, compared with controls (10% survival; 95% CI 0.04-0.45). Time of death ranged between 6 and 13 minutes in nonsurvivors. Overall comparison of survival time revealed a statistically significant improvement in experimental groups compared with controls (P < 0.0001). Pretreatment with parenteral ophthalmic solutions (tropicamide or cyclopentolate) was equivalent to standard atropine in preventing lethality in this rat model of acute, lethal OP poisoning.

A five-year review of the medical outcome of heroin body stuffers.

The medical outcome of heroin body stuffers has rarely been described. This study was performed to illustrate the clinical course of heroin body stuffers. A retrospective chart analysis was performed on all cases of heroin body stuffers received by a metropolitan poison control center from 2000-2004. We identified 65 heroin body stuffers. Sixty-nine percent were men with a mean age of 35 years. The stated quantity of heroin containers ingested ranged from 1 to 30, with 65% reported as being wrapped in plastic. Six patients (9.2%) developed symptoms of opiate intoxication. All symptoms began within an hour after the ingestion. Three patients (4.6%) needed naloxone. The mean length of observation was 24 h. Opiate intoxication from heroin stuffing is uncommon. Those patients that developed symptoms did so early in their course. These data indicate a benign clinical course in most heroin body stuffers.

Universal versus selective iron supplementation for infants and the risk of unintentional poisoning in young children: a comparative study of two populations.

BACKGROUND: Iron continues to be a common cause of poisoning in young children, in part due to its widespread use and easy accessibility. OBJECTIVE: To determine differences in the epidemiology and outcome of unintentional iron ingestion by young children in populations practicing selective (eg, US) versus universal (eg, Israel) iron supplementation to infants. METHODS: All cases of unintentional iron ingestion in children younger than 7 years in a one year period were identified through the poison control center databases of 2 sites (Illinois and Israel). Parameters compared include patient sex and age; type, form, and dose of iron preparation; circumstances and clinical manifestations; management; and outcome. RESULTS: A total of 602 children were identified: 459 in Illinois and 143 in Israel. The majority of Illinois children ingested multivitamin preparations (94%), whereas Israeli children ingested single-ingredient iron preparations (78%) (p < 0.001). Iron doses ingested were higher in Israel (median 14.5 vs 6.6 mg/kg; p < 0.001) but remained within the nontoxic range for most children. No deaths or severe poisonings were reported, and 93% of children in both groups were asymptomatic. The majority of ingestions in both locations were due to unintentional self-ingestion. However, parental miscalculation occurred more frequently in Israel (16%) than in Illinois (1%). CONCLUSIONS: Universal iron supplementation to infants was not associated with a negative impact on the outcome of pediatric unintentional ingestions. Low-dose exposures were safely managed by on-site observation.