A Retrospective Evaluation of Adjunctive Phenobarbital vs. Benzodiazepine Alone for the Treatment of Moderate Alcohol Withdrawal in the Emergency Department.

BACKGROUND: Phenobarbital has been used in the emergency department (ED) as both a primary and adjunctive medication for alcohol withdrawal, but previous studies evaluating its impact on patient outcomes are limited by heterogenous symptom severity. OBJECTIVES: We compared the clinical outcomes of ED patients with moderate alcohol withdrawal who received phenobarbital, with or without benzodiazepines, with patients who received benzodiazepine treatment alone. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of ED patients with moderate alcohol withdrawal between 2015 and 2020. Patient encounters were classified into two treatment categories based on medication treatment: phenobarbital alone or in combination with benzodiazepines vs. benzodiazepines alone. Chi-square test or Fisher's exact was used to analyze categorical variables and the Student's t-test for continuous data. RESULTS: Among the 287 encounters that met inclusion criteria, 100 received phenobarbital, compared with 187 that received benzodiazepines alone. Patients who received phenobarbital were provided significantly more lorazepam equivalents. There was a significant difference in the percentage of patient encounters that required admission to the hospital in the phenobarbital cohort compared with the benzodiazepine cohort (75% vs. 43.3%, p < 0.001). However, there was no difference in admission level of care to the floor (51.2% vs. 52.0%), stepdown (33.8% vs. 28%), or intensive care unit (15% vs. 20%), respectively. CONCLUSIONS: Patients who received phenobarbital for moderate alcohol withdrawal were more likely to be admitted to the hospital, but there was no difference in admission level of care when compared with patients who received benzodiazepines alone. Patients who received phenobarbital were provided greater lorazepam equivalents in the ED.

Scoring the best deal: Quantity discounts and street price variation of diverted oxycodone and oxymorphone.

PURPOSE: Diverted prescription opioids are significant contributors to drug overdose mortality. Street price has been suggested as an economic metric of the diverted prescription opioid black market. This study examined variables that may influence the street price of diverted oxycodone and oxymorphone. METHODS: A cross-sectional study was conducted utilizing data from the previously validated, crowdsourcing website StreetRx. Street price reports of selected oxycodone and oxymorphone products, between August 22, 2014 and June 30, 2016, were considered for analysis. Geometric means and 95% confidence intervals were calculated comparing prices per milligram of drug in US dollars. Univariate and multivariable regressions were used to examine the influence of dosage strength, drug formulation, and bulk purchasing on street price. RESULTS: A total of 5611 oxycodone and 1420 oxymorphone reports were analyzed. Across various dosages and formulations, geometric mean prices per milligram ranged between $0.12 and $1.07 for oxycodone and $0.73 and $2.90 for oxymorphone. For a 2-fold increase in dosage strength, there is a 24.0% (95% CI: -28.1%, -19.6%, P < 0.001) and a 22.5% (95% CI: -24.2%, -20.8%, P < 0.001) decrease on average in price per milligram for oxycodone and oxymorphone, respectively. Lower potency, high dosage strength, crush-resistant opioids, and those purchased in bulk were significantly cheaper. CONCLUSION: Street prices for diverted oxycodone and oxymorphone are influenced by multiple factors including potency, dosage, formulation, and bulk purchasing. Buyers who purchase large quantities of low potency, large dosage, crush-resistant formulation prescription opioids can expect to achieve the lowest price.

Serum iron concentrations in non-iron induced acute liver injury.

Acute liver injury (ALI) is seen in conjunction with elevated iron concentrations in the setting of acute iron toxicity. However, occult or delayed presentations of iron toxicity can be difficult to identify clinically and there is limited data describing iron concentrations in ALI without a confirmed history of iron overdose. This was a single center observational before-and-after study of adult patients who developed acute liver injury during hospitalization. Patients with a serum ALT > 500 U/L were identified by a daily hospital laboratory report and met inclusion if the ALT< 80 U/L at the time of admission, no history of overdose (iron, acetaminophen, or other ingestion), and no underlying liver disease. Serum AST, iron, and ferritin concentrations were obtained from blood samples at the time of admission and at peak serum ALT. Ten patients met inclusion criteria. The median age was 69 years old and 60% were male. There was a significant difference in serum AST (p = 0.005), serum ALT (p = 0.005), and ferritin (p = 0.005) before and after development of ALI. Serum iron concentrations were not clinically or significantly different (median: 23 mcg/dL vs 27 mcg/dL, p = 0.8). In this cohort of patients with non-iron induced acute liver injury, serum iron concentrations did not significantly change with the observed rise in aminotransferases. These data help to further characterize patterns of serum iron concentrations in patients with ALI.

Return Encounters in Emergency Department Patients Treated with Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal.

INTRODUCTION: Phenobarbital has been successfully used in the emergency department (ED) to manage symptoms of alcohol withdrawal, but few studies have reported outcomes for ED patients who receive phenobarbital and are discharged. We compared return encounter rates in discharged ED patients with alcohol withdrawal who were treated with benzodiazepines and phenobarbital. METHODS: This is a retrospective cohort study conducted at a single academic medical center utilizing chart review of discharged ED patients with alcohol withdrawal from July 1, 2016, to June 30, 2019. Patients were stratified according to ED management with benzodiazepines, phenobarbital, or a combination of both agents. The primary outcome was return ED encounter within three days of the index ED encounter. Multivariate logistic regression identified significant covariates of an ED return encounter. RESULTS: Of 470 patients who were discharged with the diagnosis of alcohol withdrawal, 235 were treated with benzodiazepines, 133 with phenobarbital, and 102 with a combination of both. Baseline characteristics were similar among the groups. However, patients who received phenobarbital were provided significantly more lorazepam equivalents compared to patients who received benzodiazepines alone. Treatment with phenobarbital, alone or in combination with benzodiazepines, was associated with significantly lower odds of a return ED visit within three days compared with benzodiazepines alone [AOR 0.45 (95% CI 0.23, 0.88) p = 0.02 and AOR 0.33 (95% CI 0.15, 0.74) p = 0.007]. CONCLUSIONS: Patients who received phenobarbital for alcohol withdrawal were less likely to return to the ED within three days of the index encounter. Despite similar baseline characteristics, patients who received phenobarbital, with or without benzodiazepines, were provided greater lorazepam equivalents the ED.

Circulating miR-122 in patients with non-toxic acute acetaminophen ingestions.

Introduction: MicroRNA-122 (miR-122) is a novel biomarker of liver injury and has been proposed as an early predictor of acetaminophen-associated hepatotoxicity. However, there is little data on miR-122 in patients with nontoxic acute acetaminophen ingestions.Methods: This was an observational study of patients with a history of acute acetaminophen ingestion and measured acetaminophen concentrations below the treatment nomogram and who did not receive antidotal treatment. Fold increase in miR-122 expression was measured from the remnant sample corresponding with the timed serum acetaminophen concentration used to determine need for antidotal treatment.Results: Ten patients met inclusion criteria with a four-hour acetaminophen concentration below the nomogram line (mean: 73.4 µg/mL). There was no significant difference in mean fold change of miR-122 expression between the acetaminophen exposed patients and negative controls [(0.82, IQR: 0.27, 0.77) vs (1.24, IQR: 0.54, 1.98), p = 0.33].Conclusion: miR-122 was not elevated in patients with acute acetaminophen ingestions with timed acetaminophen concentrations below the nomogram line. These data help to further characterize patterns of miR-122 in patients with acute acetaminophen exposures.

Plasma matrix metalloproteinase-9 response to eccentric exercise of the elbow flexors.

Recent efforts to establish a role for plasma matrix metalloproteinase-9 (MMP-9) as a marker of exercise-induced muscle damage have been inconsistent. Methodological and experimental design issues have contributed to confusion in this area. The purpose of this study was to use a damaging eccentric arm task to evaluate the relationship between activity-induced muscle damage and plasma MMP-9 levels in humans while controlling for physical activity history and quantifying day-to-day variability of the dependent variables. Fourteen physically inactive males performed 6 sets of 10 eccentric contractions of the elbow flexors at 120% of their voluntary concentric maximum. Soreness ratings, maximum voluntary isometric strength, range of motion (ROM), limb circumference, and plasma creatine kinase (CK) and MMP-9 levels were measured at 2 time points before, immediately after, and 1, 2, 4, and 7 days post-exercise. Changes in traditional markers of muscle damage mirrored patterns previously reported in the literature, but plasma MMP-9 concentration and activity measured by ELISA and gelatin zymography were unchanged at all time points examined. Plasma levels of the MMP-9 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), were also unchanged post-exercise. Finally, although mean MMP-9 levels were not significantly different between the two pre-exercise timepoints, the high total error of measurement and low day-to-day correlation suggest substantial within and between subject variability. Plasma MMP-9 levels are not a robust or reliable marker for eccentric exercise-induced damage of the elbow flexor musculature, though this may not preclude a role for MMPs in skeletal muscle remodeling in response to injury.

Brief Review of Chloroquine and Hydroxychloroquine Toxicity and Management.

As of April 21, 2020, more than 2.5 million cases of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, have been reported in 210 countries and territories, with the death toll at 171,810. Both chloroquine and hydroxychloroquine have gained considerable media attention as possible therapies, resulting in a significant surge in demand. In overdose, both medications can cause severe, potentially life-threatening effects. Here, we present a brief overview of the pharmacology of chloroquine and hydroxychloroquine, manifestations of toxicity, and treatment considerations.

Reversal of Pediatric Opioid Toxicity with Take-Home Naloxone: a Case Report.

BACKGROUND: Take-home naloxone, an opioid antagonist, has become part of a multimodal approach to curbing opioid-related mortality. However, there is little information about the utility of take-home naloxone in pediatric patients. We report a case of opioid toxicity after exposure to methadone in a pediatric patient, which was successfully reversed with take-home naloxone. CASE: A previously healthy 22-month-old girl ingested an unknown amount of liquid methadone. The child became progressively somnolent. The mother administered intranasal naloxone at home with reversal of somnolence. The patient presented to the emergency department and had recurrence of symptoms. The patient was placed on a naloxone infusion and discharged from a tertiary care facility, uneventfully, 2 days after ingestion. RESULTS: To our knowledge, we report the first case of pediatric opioid toxicity reversed by take-home naloxone. In the setting of rising opioid-related mortality, providers and public health officials should consider expanding access of take-home naloxone for children at high risk for opioid overdose.

Crataegus mexicana (Tejocote) Exposure Associated with Cardiotoxicity and a Falsely Elevated Digoxin Level.

INTRODUCTION: A species of hawthorn, Crataegus mexicana (tejocote), has been marketed as a weight-loss supplement that is readily available for purchase online. While several hawthorn species have shown clinical benefit in the treatment of heart failure owing to their positive inotropic effects, little is known about hawthorn, and tejocote in particular, when consumed in excess. We describe a case of tejocote exposure from a weight-loss supplement resulting in severe cardiotoxicity. CASE REPORT: A healthy 16-year-old girl presented to an emergency department after ingesting eight pieces of her mother's tejocote root weight-loss supplement. At arrival, she was drowsy, had active vomiting and diarrhea, and had a heart rate of 57 with normal respirations. Her initial blood chemistries were unremarkable, except for an elevated digoxin assay of 0.7 ng/mL (therapeutic range 0.5-2.0 ng/mL). All other drug screens were negative. She later developed severe bradycardia and multiple episodes of hypopnea that prompted a transfer to our institution, a tertiary pediatric hospital. Her ECG demonstrated a heart rate of 38 and Mobitz type 1 second-degree heart block. She was subsequently given two vials of Digoxin Immune Fab due to severe bradycardia in the setting of suspected digoxin-like cardiotoxicity after discussion with the regional poison control center. No clinical improvement was observed. Approximately 29 hours after ingestion, subsequent ECGs demonstrated a return to normal sinus rhythm, and her symptoms resolved. DISCUSSION: Tejocote root toxicity may cause dysrhythmias and respiratory depression. Similar to other species of hawthorn, tejocote root may cross-react with some commercial digoxin assays, resulting in a falsely elevated level.

Psychiatric Outcomes of Patients With Severe Agitation Following Administration of Prehospital Ketamine.

BACKGROUND: Ketamine is an emerging drug used in the management of undifferentiated, severe agitation in the prehospital setting. However, prior work has indicated that ketamine may exacerbate psychotic symptoms in patients with schizophrenia. The objective of this study was to describe psychiatric outcomes in patients who receive prehospital ketamine for severe agitation. METHODS: This is a retrospective cohort study, conducted at two tertiary academic medical centers, utilizing chart review of patients requiring prehospital sedation for severe agitation from January 1, 2014, to June 30, 2016. Patients received either intramuscular (IM) versus intravenous (IV) ketamine or IM versus IV benzodiazepine. The primary outcome was psychiatric inpatient admission with secondary outcomes including ED psychiatric evaluation and nonpsychiatric inpatient admission. Generalized estimating equations and Fisher's exact tests were used to compare cohorts. RESULTS: During the study period, 141 patient encounters met inclusion with 59 (42%) receiving prehospital ketamine. There were no statistically significant differences between the ketamine and benzodiazepine cohorts for psychiatric inpatient admission (6.8% vs. 2.4%, difference = 4.3%, 95% CI = -2% to 12%, p = 0.23) or ED psychiatric evaluation (8.6% vs. 15%, difference = -6.8%, 95% CI = -18% to 5%, p = 0.23). Patients with schizophrenia who received ketamine did not require psychiatric inpatient admission (17% vs. 10%, difference = 6.7%, 95% CI = -46% to 79%, p = 0.63) or ED psychiatric evaluation (17% vs. 50%, difference = -33%, 95% CI = -100% to 33%, p = 0.55) significantly more than those who received benzodiazepines, although the subgroup was small (n = 16). While there was no significant difference in the nonpsychiatric admission rate between the ketamine and benzodiazepine cohorts (35% vs. 51%, p = 0.082), nonpsychiatric admissions in the benzodiazepine cohort were largely driven by intubation (63% vs. 3.8%, difference = 59%, 95% CI = 38% to 79%, p < 0.001). CONCLUSIONS: Administration of prehospital ketamine for severe agitation was not associated with an increase in the rate of psychiatric evaluation in the emergency department or psychiatric inpatient admission when compared with benzodiazepine treatment, regardless of the patient's psychiatric history.

Clozapine Intoxication Mimicking Acute Stroke.

Clozapine is an atypical antipsychotic drug prescribed for treatment-resistant schizophrenia. The risk of adverse hematologic, cardiovascular, and neurologic effects has tempered its use, and reports of overdoses remain rare. We report a case of accidental acute clozapine intoxication in a clozapine-naïve patient, who presented with symptoms mimicking acute stroke and later developed status epilepticus. Clozapine intoxication is a rare presentation in the emergency department with potential for iatrogenic harm if not correctly identified.

Comparative Rates of Mortality and Serious Adverse Effects Among Commonly Prescribed Opioid Analgesics.

INTRODUCTION: The epidemic of prescription opioid overdose and mortality parallels the dispensing rates of prescription opioids, and the availability of increasingly potent opioid analgesics. OBJECTIVE: The common assumption that more potent opioid analgesics are associated with higher rates of adverse outcomes has not been adequately substantiated. We compared the rate of serious adverse events among commonly prescribed opioid analgesics of varying potency. METHODS: Serious adverse events (SAEs; defined as death, major medical effect, or hospitalization) resulting from exposure to tablets containing seven opioid analgesics (oxycodone, hydrocodone, morphine, hydromorphone, oxymorphone, tapentadol, and tramadol) captured by the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS®) System Poison Center Program were evaluated from 2010 through 2016. Rates of SAEs were adjusted for availability through outpatient dispensing data and regressed on morphine milligram equivalents (MME). RESULTS: There were 19,480 cases of SAE during the 7-year study period. Hydrocodone and oxycodone contributed to 77% of SAE cases. Comparing rates of outcome by relative potency, a hierarchy was observed with hydromorphone (8.02 SAEs/100 kg) and tapentadol (0.27 SAE/100 kg) as the highest and lowest rates, reflecting a 30-fold difference among individual opioid products. SAE rate and potency were related linearly-SAEs increased 2.04 per 100 kg drug dispensed for each 1-unit rise in MME (p = 0.004). Linear regression of SAE/100 kg drug dispensed and drug potency identified that MME comprised 96% of the variation observed. In contrast, potency did not explain variation seen using other study denominators (prescriptions dispensed, dosage units dispensed, and the number of individuals filling a prescription). CONCLUSIONS AND RELEVANCE: Potency of a prescription opioid analgesic demonstrates a significant, highly positive linear relationship with exposures resulting in SAEs per 100 kg drug dispensed reported to poison centers. Potency should be carefully considered from both individual provider and public health perspectives.