Practices and Outcomes Associated With Sublingual Buprenorphine Use in a Critically Ill Population.

IMPORTANCE: Buprenorphine for opioid use disorder (OUD) is commonly used in the outpatient setting with increasing use in hospitalized patients. However, there is limited literature describing its use in critically ill populations. OBJECTIVES: The primary objective was to report the practices of buprenorphine prescribing among ICU teams. We also assessed the effect of a novel initiation strategy on opioid requirements in the ICU and the incidence of precipitated withdrawal. DESIGN SETTING PARTICIPANTS: Single-center, retrospective, descriptive study of patients receiving buprenorphine in the ICU. MAIN OUTCOMES AND MEASURES: The main outcome was to describe the use of buprenorphine in ICU patients through indication, initiation strategy, dosing information, and time from ICU admission to the first dose. We also detailed the incidence of precipitated withdrawal overall and the difference in opioid requirements before and after a low-dose induction strategy (buprenorphine initiated while receiving full agonist opioids [5-d titration from 150 µg to 4 mg four times daily]). RESULTS: A total of 153 patients were included. Most patients (86.3%) received buprenorphine for treatment of OUD. Of the 75 patients taking buprenorphine before admission, 46 (61%) had it restarted within 24 hours of ICU admission. Among 95 patients requiring buprenorphine induction, 57 (60%) underwent standard induction and 38 (40%) underwent low-dose induction, with only one instance of precipitated withdrawal. Median morphine milligram equivalents (MMEs) of concomitant full agonist opioids in patients completing low-dose induction decreased from 1057.5 mg to 262.5 mg in the 24 hours before initiation compared with the 24 hours after target buprenorphine dose was reached (p < 0.005). CONCLUSIONS AND RELEVANCE: Use of sublingual buprenorphine was most often in patients with OUD. Timely continuation of home buprenorphine in the ICU was suboptimal. Both standard and low-dose induction strategies appear to be safe with a low risk of precipitating withdrawal. When implemented appropriately, low-dose buprenorphine induction may lead to significant reduction in full agonist opioids in critically ill patients.

Evaluation of hydroxocobalamin use for the treatment of suspected cyanide toxicity secondary to smoke inhalation.

Hydroxocobalamin is used for cyanide toxicity after smoke inhalation, but diagnosis is challenging. Retrospective studies have associated hydroxocobalamin with acute kidney injury (AKI). This is a retrospective analysis of patients receiving hydroxocobalamin for suspected cyanide toxicity. The primary outcome was the proportion of patients meeting predefined appropriate use criteria defined as ≥1 of the following: serum lactate ≥8 mmol/L, systolic blood pressure (SBP) <90 mmHg, new-onset seizure, cardiac arrest, or respiratory arrest. Secondary outcomes included incidence of AKI, pneumonia, resolution of initial neurologic symptoms, and in-hospital mortality. Forty-six patients were included; 35 (76%) met the primary outcome. All met appropriate use criteria due to respiratory arrest, 15 (43%) for lactate, 14 (40%) for SBP, 12 (34%) for cardiac arrest. AKI, pneumonia, and resolution of neurologic symptoms occurred in 30%, 21%, and 49% of patients, respectively. In-hospital mortality was higher in patients meeting criteria, 49% vs. 9% (95% CI 0.16, 0.64). When appropriate use criteria were modified to exclude respiratory arrest in a post-hoc analysis, differences were maintained, suggesting respiratory arrest alone is not a critical component to determine hydroxocobalamin administration. Predefined appropriate use criteria identify severely ill smoke inhalation victims and provides hydroxocobalamin treatment guidance.

Generalized seizures after acute fluoxetine overdose in four adolescents.

Fluoxetine is a selective serotonin reuptake inhibitor that is less frequently associated with severe toxicity in acute overdose compared with other psychotropic medications. Although rare, generalized seizure has been reported after isolated fluoxetine overdose. Most cases in the literature have occurred between one- and 16 h following acute ingestion of ≥1000 mg. Here, we present a series of four cases of adolescents who presented to our pediatric emergency department with reported or witnessed seizures after acute fluoxetine overdose between 3/2021 and 1/2022. These cases included intentional ingestions of fluoxetine at doses between 600 and 1200 mg (10-19.5 mg/kg), each of whom had a single, witnessed episode of generalized seizure activity which occurred between three- and nine-hours post-ingestion. All patients had signs of mild serotonin excess and two met conventional criteria for diagnosis of serotonin toxicity. All patients were evaluated by a medical toxicologist and were hospitalized for observation. No patient developed subsequent seizure or further complications related to overdose and no patient received neuroimaging, electroencephalography, or evaluation by a neurologist. Though previously described, seizure is an uncommon and potentially underappreciated complication after fluoxetine overdose and occurred in some of our patients at doses lower than those which have typically been reported in the literature.

Low-dose Initiation of Buprenorphine in Hospitalized Patients on Full Agonist Opioid Therapy: A Retrospective Observational Study.

OBJECTIVE: Buprenorphine can be challenging to initiate in hospitalized patients with opioid dependence because of difficulty tolerating an opioid-free period for buprenorphine induction. The objective of this study was to evaluate efficacy and safety of low-dose initiation of buprenorphine in hospitalized patients receiving full agonist opioids. METHODS: This is a retrospective observational study between January 1, 2019, and December 31, 2020, at an academic tertiary care center and affiliated community hospital. Participants included adult patients at least 18 years old receiving scheduled full agonist opioids who were given sublingual buprenorphine 0.5 mg or less with the intent of increasing to at least 4 mg daily. The primary endpoint was the proportion of patients reaching a target dose of at least 4 mg total per day. The secondary endpoints included the incidence of precipitated opioid withdrawal based on documentation of symptoms and change in morphine milligram equivalents before and after low-dose buprenorphine initiation. RESULTS: A total of 76 low-dose initiation attempts were performed in 71 predominantly male (68%) patients (some patients had multiple attempts). Most patients received low-dose initiation because of history of opioid use disorder (83%). Low-dose initiation was completed in 54 of 71 patients (76%) after 76 attempts. Precipitated withdrawal was identified in 2 patients (2.8%). Median morphine milligram equivalents excluding buprenorphine 24 hours before low-dose initiation was 1000 mg (interquartile range, 303.5-1720.5 mg) compared with 37.5 mg (interquartile range, 0-254 mg) after reaching target dose ( P < 0.001). CONCLUSIONS: Buprenorphine was safely initiated using low-dose initiation in hospitalized patients. This was associated with significant reduction in full agonist opioids.

Profound Hyperthermia Associated With Fentanyl and Cocaine Use With Suspected Synephrine Adulteration.

BACKGROUND: Although hyperthermia is described after cocaine intoxication, the two hyperthermic cases discussed were unusual in severity and duration for cocaine alone. Synephrine was found in biological samples of these patients in high concentrations and was suspected to be an adulterant in illicitly obtained drugs. CASE REPORT: Two patients presented to a tertiary care university hospital within 2 days of each other after recreational drug use with delayed and protracted hyperthermia. Synephrine was later found in high concentrations in biological samples as an unexpected drug adulterant. The first patient's presentation came with delayed recognition of hyperthermia and implementation of aggressive cooling measures; he entered multisystem organ failure with prolonged intensive care unit stay and significant morbidity. The second patient's hyperthermia was recognized promptly, and she received early, aggressive cooling, including deep sedation and ice water submersion. She left against medical advice from the hospital at her baseline 3 days after presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Synephrine is a suspected adulterant that may be associated with profound hyperthermia. Early recognition of drug overdose and working knowledge of common adulterants can facilitate early targeted management, such as aggressive cooling measures, which may prevent morbidity and mortality.

Evaluation of high-dose insulin/euglycemia therapy for suspected ß-blocker or calcium channel blocker overdose following guideline implementation.

PURPOSE: High-dose insulin/euglycemia (HDIE) is targeted therapy for ß-blocker and calcium channel blocker overdose. A guideline using concentrated insulin infusions (20 units/mL), aggressive monitoring, and supportive recommendations was implemented. We sought to evaluate safety before and after HDIE guideline implementation and describe the patient population, insulin doses, supplemental dextrose, vasopressor use, hospital and intensive care unit (ICU) lengths of stay, and mortality. METHODS: Retrospective review was performed of patients receiving HDIE before and after guideline implementation at an academic medical center and community hospital from March 2011 through December 2019. Information on patient and overdose demographics, ingestion data, vital signs, interventions, adverse events, and disposition was collected. Data are presented descriptively with comparisons using Mann-Whitney U analysis and Fisher's exact tests. RESULTS: During the study period, 27 patients were treated with HDIE, 10 before guideline implementation (37%; mean [SD] initial insulin dose, 0.49 [0.35] units/kg/h; mean [SD] maximum insulin dose, 2.25 [3.29] units/kg/h; median [interquartile range] duration, 10 [5.5-18.75] hours) and 17 after guideline implementation (63%; mean [SD] initial insulin dose, 1.01 [0.34] units/kg/h; mean [SD] maximum insulin dose, 2.99 [5.05] unit/kg/h; median [interquartile range] duration, 16 [11.5-37] hours). Hypoglycemia, hypokalemia, and volume overload occurred in 80% vs 29% (P = 0.018), 40% vs 53% (P = 0.69), and 50% vs 65% (P = 0.69) of patients in the preguideline vs postguideline group, respectively. Most patients received an initial insulin bolus (85%; mean [SD], 70.3 [21.8] units, 0.9 [0.26] units/kg) and vasopressor infusion (85%). More postguideline patients received a dextrose infusion with a concentration of 20% or higher (93% vs 50%, P = 0.015). There were no differences in cardiac arrest, in-hospital mortality, or hospital or ICU length of stay between the groups. CONCLUSION: Hypoglycemia was reduced using an HDIE guideline and concentrated insulin.

Amphetamine and Clonidine Toxicity Resulting in Posterior Reversible Encephalopathy Syndrome.

ABSTRACT: Amphetamine toxicity typically presents with hypertension and tachycardia. Conversely, clonidine acts as an agonist at central α2 and imidazoline receptors, which may cause brief initial hypertension followed by hypotension and bradycardia in overdose. We report a case of mixed ingestion resulting in posterior reversible encephalopathy syndrome (PRES) successfully treated with phentolamine.A 17-year-old male adolescent presented to the emergency department 2 hours after ingesting up to 25 each of clonidine 0.1-mg tablets and dextroamphetamine 10 mg extended-release capsules. He reported nausea and fatigue with initial blood pressure (BP) 145/95 mm Hg and heart rate (HR) 52 beats per minute (bpm). Nine hours postingestion (HPI), the patient developed headache, photophobia, and confusion with BP 182/111 mm Hg and HR 48 bpm. A computed tomography scan of the head revealed generalized fullness of the cerebellum, upward bulging of the tentorial leaflets, effacement of the fourth ventricle, and crowding of the foramen magnum, suspicious for an atypical presentation of PRES. The patient's systolic BP rose over 200 mm Hg and treated with 2 mg of intravenous phentolamine at 14 HPI. Blood pressure decreased to 133/82 mm Hg, and HR increased to 56 bpm with improvements in headache. Following repeat doses of phentolamine, nicardipine was initiated and increased to 2.5 mg/h for 12 hours. The patient was stable with normal vital signs at 36 HPI.The delayed presentation of hypertensive emergency with PRES may have been due to the actions of extended-release dextroamphetamine and the α2-agonistic effects of clonidine. Phentolamine was chosen for its α1-antagonism and was effective in managing symptoms.

Emergency Medicine Intern Education for Best Practices in Opioid Prescribing.

INTRODUCTION: Opioid exposure has been identified as a contributing factor to the opioid epidemic. Reducing patient exposure, by altering heavy opioid prescribing patterns but appropriately addressing patient pain, may represent one approach to combat this public health issue. Our goal was to create and implement an opioid education program for emergency medicine (EM) interns as a means of establishing foundational best practices for safer and more thoughtful prescribing. METHODS: This was a retrospective study at an academic, urban emergency department (ED) comparing ED and discharge opioid prescribing practices over a 12-week time period for two 14-intern EM classes (2016 and 2018) to evaluate an early opioid reduction education program. The education program included opioid prescribing guidelines for common ED disease states associated with moderate pain, clinician talking points, and electronic education modules, and was completed by EM interns in July/August 2018. Opioid prescription rates per shift were calculated and opioid prescribing best practices described. We used chi-squared analysis for comparisons between the 2016 and 2018 classes. RESULTS: Overall, ED and discharge opioid orders prescribed by EM interns were fewer in the 2018 class that received education compared with the 2016 class. ED opioid orders were reduced by 64% (800 vs 291 orders, rate per shift 1.8 vs 0.7 orders) and opioid discharge prescriptions by 75% (279 vs 70 prescriptions, rate per shift 0.7 vs 0.2 prescriptions). The rate of prescribing combination opioid products compared to opioids alone was decreased for ED orders (32% vs 16%, P < 0.01) and discharge prescriptions (91% vs 74%, P < 0.01) between the groups. Also, the median tablets per discharge prescription (14.5 vs 10) and total tablets prescribed (4305 vs 749) were reduced, P < 0.01. There were no differences in selection of opioid product or total morphine milligram equivalents prescribed when an opioid was used. CONCLUSION: An opioid reduction education program targeting EM interns was associated with a reduction in opioid prescribing in the ED and at discharge. This may be an effective way to influence early prescribing patterns and best practices of EM interns.

Kratom Adulterated with Phenylethylamine and Associated Intracerebral Hemorrhage: Linking Toxicologists and Public Health Officials to Identify Dangerous Adulterants.

INTRODUCTION: Kratom is derived from the plant Mitragyna speciosa which is indigenous to Southeast Asia. Active compounds, mitragynine and 7-hydroxymitragynine, cause mild stimulant and opioid agonist effects. Although reported to have potential benefits in the treatment of opioid use disorder, efficacy remains uncertain while adverse health effects have been reported. A compounding concern is the presence of adulterants given that this is an unregulated product. CASE DETAILS: A 54-year-old fitness instructor who used an online purchased kratom product regularly for one year developed stimulatory effects and suffered a large hemorrhagic stroke with a close temporal relationship to ingestion of a different kratom product from the one he regularly used. A collaborative investigation by medical toxicologists, a regional poison center, the state public health laboratory, and public health officials determined that his new kratom product was adulterated with phenylethylamine (PEA). DISCUSSION: We report a case of PEA adulterated kratom purchased and used with resultant adverse effects. PEA is structurally similar to amphetamine and is known to produce sympathomimetic effects. It is possible the stimulatory effect of PEA resulted in a marked and transient increase in blood pressure resulting in hemorrhagic stroke. CONCLUSION: Medical toxicologists should form working relationships with laboratories and public health officials to aid in early identification of adulterated products that carry risk to the general population.

Effect of pharmacist-led task force to reduce opioid prescribing in the emergency department.

PURPOSE: Results of a study to determine the effect of a pharmacist-led opioid task force on emergency department (ED) opioid use and discharge prescriptions are presented. METHODS: An observational evaluation was conducted at a large tertiary care center (ED volume of 115,000 visits per year) to evaluate selected opioid use outcomes before and after implementation of an ED opioid reduction program by interdisciplinary task force of pharmacists, physicians, and nurses. Volumes of ED opioid orders and discharge prescriptions were evaluated over the entire 25-month study period and during designated 1-month preimplementation and postimplementation periods (January 2017 and January 2018). Opioid order trends were evaluated using linear regression analysis and further investigated with an interrupted time series analysis to determine the immediate and sustained effects of the program. RESULTS: From January 2017 to January 2018, ED opioid orders were reduced by 63.5% and discharge prescriptions by 55.8% from preimplementation levels: from 246.8 to 90.1 orders and from 85.3 to 37.7 prescriptions per 1,000 patient visits, respectively. Over the entire study period, there were significant decreases in both opioid orders (ß, -78.4; 95% confidence interval [CI], -88.0 to -68.9; R2, 0.93; p < 0.0001) and ED discharge prescriptions (ß, -24.4; 95% CI, -27.9 to -20.9; R2, 0.90; p < 0.001). The efforts of the task force had an immediate effect on opioid prescribing practices; results for effect sustainability were mixed. CONCLUSION: A clinical pharmacist-led opioid reduction program in the ED was demonstrated to have positive results, with a more than 50% reduction in both ED opioid orders and discharge prescriptions.

Citalopram overdose and severe serotonin syndrome in an intermediate metabolizing patient.

INTRODUCTION: Citalopram is a selective serotonin reuptake inhibitor used for treatment of depression. Metabolism is primarily through CYP3A4 and CYP2C19; activity of the latter can vary depending on genetics. Although rare after single agent exposure, large citalopram ingestions can lead to serotonin syndrome. We report a case of citalopram overdose in an intermediate CYP2C19 metabolizer complicated by severe serotonin syndrome. CASE DETAILS: A 25-year-old female presented after intentional citalopram overdose with seizures, tachycardia, persistent neuromuscular findings, and severe hyperthermia requiring aggressive sedation and cooling. Protracted symptoms required critical care services throughout a 14 day hospital stay despite traditional treatment of serotonin syndrome. Pharmacogenomic studies revealed intermediate CYP2C19 metabolism which reduces citalopram inactivation and may cause increased levels and toxicity. DISCUSSION: In the majority of serotonin syndrome cases, symptoms resolve rapidly after treatment initiation and discontinuation of the offending agents. Severe cases are typically associated with ingestion of multiple serotonergic agents. Our patient had severe toxicity after single agent ingestion. Pharmacogenetic testing identified abnormal CYP2C19 activity and previous cases have associated enzyme dysfunction and citalopram toxicity. CONCLUSION: Citalopram overdose may be associated with severe serotonin syndrome and further investigation is warranted to understand the impact of enzyme genotype on toxicity.

Validation of the Poisoning Severity Score (PSS) in suicidal behavior by self-poisoning.

Intentional self-poisoning is the leading method of suicidal behavior leading to medical attention worldwide. The medical severity of self-poisoning events has major treatment, prognostic, and medico-legal implications, yet measures of severity are limited. The Poisoning Severity Score (PSS) is a widely used scale but validation data are limited, particularly in the study of suicidal behavior per se. The sample was a consecutive series of intentional self-poisoning patients aged 13 to 65 treated at a large university medical center (n = 673). PSS scores, with a range 0 (none) to 4 (death), were calculated along with other structured clinical data and analyzed in a series of linear regressions adjusted for age and sex. Higher PSS scores were consistently associated with greater medical morbidity and more intensive acute medical treatments, and nearly all effect sizes were large. Results support the validity of the PSS in hospital-treated self-poisoning patients.

Poisoning Severity Associated with a Range of Medications in Suicide Attempts by Ingestion.

There are limited data on the medical severity of suicide attempts by intentional self-poisoning (ISP) associated with ingestion of differing classes of medications and meager data on specific agents. The purpose of the study was to address these gaps. This was an analysis of a consecutive series of ISP cases ages 13 to 65 treated at a U.S. university medical center (N = 671). The outcome, poisoning severity, was dichotomized as "moderate-severe" and "low" (reference) based on a standard measure. Class of medication (e.g., opiate) and specific agents ingested were the predictors of interest. Covariates were age, sex, and the ingestion of multiple classes of medications. Data were analyzed using multivariate logistic regression models. At the class level, ingestion of opiate was uniquely associated with increased risk for moderate-severe ISP at a statistically significant level, adjusted odds ratio (95% CI) = 2.97 (1.69, 5.21), p = .0002. Several specific agents were also associated with moderate-severe ISP. Along with the key role of opiate medications in unintentional overdose morbidity and mortality, opiate medications may also play an important and largely unrecognized role in medically serious suicidal behavior. Results also underscore the variability in toxicity of specific agents within drug classes.

Prescription-, Illicit-, and Self-Harm Opioid Overdose Cases Treated in Hospital.

OBJECTIVE: Research suggests unintentional overdose on prescription drugs and intentional self-harm cases differ fundamentally from unintentional illicit drug overdoses, but there are few data on opioid overdose per se. METHOD: We analyzed consecutive opioid overdose patients age 13 and over (N = 435) treated by a toxicology consult service to compare three poisoning groups: unintentional illicit drug (illicit, n = 128), unintentional prescription drug (prescription, n = 217), and intentional self-harm (self-harm, n = 90). The groups were compared on key characteristics of the poisoning events (severity, co-ingestion of non-opioid) and the hospital-based treatments required to manage the poisonings (use of antidote, provision of pharmacological support). Logistic regressions yielded incident rate ratios (IRRs) and 95% confidence intervals (CI) adjusted for age and sex. RESULTS: Compared to the illicit group, the prescription group was more likely to co-ingest a non-opioid drug (IRR [95% CI] = 1.594 [1.077, 2.358], p = .020. Compared to illicit cases, self-harm cases were more likely to co-ingest a non-opioid drug (IRR = 3.181 [1.620, 6.245], p = .001) and had a lower poisoning severity score (IRR = 0.750 [0.564, 0.997], p = .048). There were no statistically significant differences between the self-harm and prescription groups. CONCLUSIONS: The similarities between the self-harm and prescription poisoning groups suggest that they may benefit from common interventions including appropriate restriction on prescription of opioids and other medications that may be misused (e.g., sedative-hypnotic/muscle relaxants). The characteristics of the illicit poisoning group (use of heroin; more severe overdose events) suggest the need for initiation of intensive substance use treatment interventions during hospitalization.

Coma, Seizures, Atrioventricular Block, and Hypoglycemia in an ADB-FUBINACA Body-Packer.

BACKGROUND: Synthetic cannabinoid intoxication has become difficult to diagnose and manage in the United States, in part due to varying clinical effects within this heterogeneous group of compounds. CASE REPORT: A 38-year-old man was admitted with altered mental status and bradycardia. He demonstrated progressive encephalopathy, seizure activity, second-degree atrioventricular block type I, respiratory failure, hypotension, hypothermia, and hypoglycemia. A computed tomography scan of the abdomen and pelvis revealed multiple packages in the patient's stomach and rectum. Multiple attempts at gastrointestinal decontamination were unsuccessful. On hospital day 8 the patient developed hypertensive emergency and was taken to the operating room for exploratory laparotomy. Twenty-two poorly wrapped packages were removed from the bowel. Postoperatively the patient demonstrated both generalized and focal seizure activity. His mental status slowly returned to baseline over the period of about 1 week and he was ultimately discharged without neurological sequelae after 1 month. Analysis of patient serum, urine, and plant matter from the packages identified cannabis and 2.N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (ADB-FUBINACA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The case presented demonstrates the suspected toxidrome associated with severe ADB-FUBINACA intoxication, including mental status depression, bradycardia, autonomic instability, seizure, hypoglycemia, and hypothermia. Although the patient had simultaneous exposure to cannabis, his constellation of symptoms is not consistent with cannabis intoxication. A previous animal model supports the potential of this specific synthetic cannabinoid to cause the reported toxidrome.