Nebulized medications in the emergency department: A narrative review of nontraditional agents.

PURPOSE: This article summarizes emerging nontraditional therapies administered via the nebulization route for use in the emergency department (ED). SUMMARY: Although traditional routes of medication administration (eg, intravenous) have been the mainstay of administration modalities for decades, these routes may not be appropriate for all patients. Nowhere is this more readily apparent than in the ED setting, where patients with a variety of presentations receive care. One unique route for medication administration that has increasingly gained popularity in the ED is that of aerosolized drug delivery. This route holds promise as direct delivery of medications to the site of action could yield a more rapid and effective therapeutic response while also minimizing systemic adverse effects by utilizing a fraction of the systemic dose. Medication administration via nebulization also provides an alternative that is conducive to rapid, less invasive access, which is advantageous in the emergent setting of the ED. This review is intended to analyze the existing literature regarding this route of administration, including the nuances that can impact drug efficacy, as well as the available literature regarding novel, noncommercial nebulized medication therapy given in the ED. CONCLUSION: Multiple medications have been investigated for administration via this route, and when implementing any of these therapies several practical considerations must be taken into account, from medication preparation to administration, to ensure optimal efficacy while minimizing adverse effects. The pharmacist is an essential bedside team member in these scenarios to assist with navigating unique and complex nuances of this therapy as they develop.

Intranasal Dexmedetomidine Use in Pediatric Patients for Anxiolysis in the Emergency Department.

OBJECTIVES: In recent years, dexmedetomidine has gained traction as a treatment for anxiolysis in the emergency department (ED). When used with an atomizer, it may also be given intranasally for anxiolysis. The primary objective was to determine the level of ED provider satisfaction and comfort with intranasal (IN) dexmedetomidine for anxiolysis in pediatric patients with behavioral agitation and/or acute psychosis. The secondary objectives included determining safety, rates of therapy failure, and ED length of stay compared with oral midazolam. The efficacy of IN dexmedetomidine versus oral midazolam in patients with autism spectrum disorder (ASD) was also evaluated. METHODS: This was a single-center, prospective study in a pediatric ED from March 1 to December 31, 2021. Patients were included in the study if the ED provider requested IN dexmedetomidine anxiolysis and completed a postadministration survey. Safety and efficacy outcomes were assessed by chart review and compared with patients who received oral midazolam during the same study period. Efficacy was defined as the rate of treatment failure, as the need for procedural termination, progression to procedural sedation, or the requirement of additional medications for anxiolysis. RESULTS: Sixty-two patients received IN dexmedetomidine {median dose [interquartile range (IQR)] of 3.05 [2.04-4.00] µg/kg/dose} compared with 58 who received oral midazolam [median (IQR) dose of 0.29 (0.25-0.48) mg/kg/dose). Providers reported high comfort and satisfaction scores, with median (IQR) scores of 90 (75-100) and 88 (60-100) of 100. Twenty-nine percent of patients experienced treatment failure, most commonly because of the need for additional medications. Those who received IN dexmedetomidine had a longer ED length of stay (6.0 vs 4.4 hours, P = 0.010). Among the patients with ASD, those who received IN dexmedetomidine had a lower rate of treatment failure compared with oral midazolam (21.2% vs 66.7%, P = 0.039). CONCLUSIONS: This study demonstrates that IN dexmedetomidine has high levels of provider comfort and satisfaction, moderately high success rate, and a promising safety profile. In addition, IN dexmedetomidine may be superior to oral midazolam in patients with ASD for anxiolysis, but additional studies are needed.

Brown recluse spider envenomation with systemic loxoscelism and delayed hemolysis: A case report.

The brown recluse spider (Loxosceles reclusa) is endemic to the South, West and Central Midwestern United States, and envenomation from this spider can cause cutaneous and/or systemic symptoms. We present a case of systemic loxocelism in an adolescent male resulting in three emergency department visits and two hospitalizations for a rare case of delayed hemolysis 6 days after envenomation. A 19-year-old male presented to the emergency department twice within two days after envenomation with worsening pain, subjective fever, chills, nausea and vomiting. He required a two-day hospitalization for rhabdomyolysis and acute kidney injury. The patient was discharged with improving symptoms and laboratory results on day four before returning again on day seven with worsening symptoms. He was diagnosed with hemolytic anemia on day seven and was subsequently hospitalized for six days. This case of systemic loxoscelism manifested hemolysis six days after envenomation, following an improvement in symptoms and laboratory studies. This case highlights the need for continuous monitoring and/or follow-up in cases of systemic loxocelism.

Intravenous phytonadione administered orally in reducing warfarin-related coagulopathy.

INTRODUCTION: The cost of phytonadione tablets has increased markedly and is significantly higher than the intravenous formulation. The intravenous formulation given orally is a potential alternative but has not been directly evaluated in comparison to the commercially available tablet. The objective of this study was to evaluate the efficacy of phytonadione intravenous solution given orally compared to commercially available phytonadione tablets for reversal of coagulopathy related to warfarin. METHODS: We conducted a retrospective, observational study of adult patients who received phytonadione tablets and the IV formulation orally for warfarin-related coagulopathy. The international normalized ratio (INR) was measured before and after phytonadione administration. The primary outcome was INR <1.5 at 24 h after phytonadione administration. RESULTS: From January 1, 2015 to August 1, 2018 a total of 200 patients were identified. In total, 58% (n = 116) patients received IV phytonadione solution given orally and 42% (n = 84) patients received the tablets. The primary outcome of INR <1.5 at 24 h was not significantly different between groups (p = 0.321). DISCUSSION: The IV phytonadione solution given by mouth and the tablet formulation performed similarly.

Sedation and Acute Encephalopathy in a Pediatric Patient Following Ingestion of Delta-8-Tetrahydrocannabinol Gummies.

BACKGROUND Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise. CASE REPORT We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg of delta-8 THC gummies. The patient arrived minimally responsive and requiring intubation for encephalopathy. Laboratory confirmation of delta-8 THC exposure is not routinely available with common testing modalities. A urine drug screen preformed in the hospital was positive for delta-9 THC. With the collaboration of the Drug Enforcement Administration's Toxicology Testing Program, detection and confirmation of delta-8 THC was performed in the serum and urine using liquid chromatography-quadrupole time-of-flight mass spectrometry. CONCLUSIONS The prevalence of delta-8 THC-containing products in the illicit drug market is increasing rapidly. Delta-8 THC products are now available in gas stations and in headshops. The clinical presentation of delta-8 THC exposure is similar to known effects of delta-9 THC exposure. These similarities limit the clinicians' abilities to determine the specific substance ingested. Symptomatic and supportive care remains an effective treatment for cannabinoid toxicity.

Evaluation of Dosing Strategies of N-acetylcysteine for Acetaminophen Toxicity in Patients Greater than 100 Kilograms: Should the Dosage Cap Be Used?

INTRODUCTION: Acetaminophen is a commonly used analgesic and antipyretic, with the potential to cause significant injury when ingested in toxic amounts. Although the antidote n-acetylcysteine (NAC) is available, evidence supporting dose recommendations for patients weighing over 100 kg are lacking. We performed a retrospective, multi-center analysis to determine if a capped NAC dosing scheme is similar to a non-capped dosing scheme in patients weighing over 100 kg. METHODS: Between January 2009 and January 2016, we identified patients presenting to 12 different centers who were evaluated for acetaminophen poisoning treatment. Patients must have weighed greater than 100 kg and were evaluated and identified as needing treatment for acetaminophen-related poisoning with NAC. The primary outcome was occurrence of hepatic injury, defined as an AST or ALT ≥ 100 IU/L. Secondary endpoints included number of drug-related adverse events, occurrence of hepatotoxicity, cumulative NAC dose, regimen cost, length of hospital and intensive care unit stays, and in-hospital mortality. RESULTS: There were 83 patients identified as meeting the pre-specified inclusion and exclusion criteria. A capped NAC dosing scheme resulted in no difference in hepatic injury when compared to a non-capped regimen (49.4% vs 50%, p = 1.000). The capped dosage regimen was associated with a lower cumulative dose (285.2 mg/kg vs 304.6 mg/kg, p < 0.001) and cost. No other statistically significant differences were identified among the secondary endpoints. CONCLUSION: A capped NAC dosing scheme was not associated with higher rates of hepatic injury or hepatotoxicity in obese patients in the setting of acetaminophen poisoning when compared to a non-capped regimen. Further research is needed to verify these results.

Use of Intranasal Ketamine in Pediatric Patients in the Emergency Department.

OBJECTIVES: Ketamine is a safe and widely used sedative and analgesic in the pediatric emergency department (ED). The use of intranasal (IN) ketamine in exchange for the administration of intravenous sedatives or analgesics for procedural sedation in pediatric patients is not commonplace. The goal of this study was to evaluate provider perceptions and patient outcomes at varying doses of IN ketamine for anxiolysis, agitation, or analgesia. METHODS: From January 2018 to May 2018, we performed a prospective survey and chart review of pediatric patients receiving IN ketamine. The primary outcome was to determine provider satisfaction with using IN ketamine. Secondary objectives included comparing outcomes stratified by dose, adverse events, assessing for treatment failure, and ED length of stay (LOS). As a secondary comparison, patients receiving IN ketamine whom otherwise would have required procedural sedation with intravenous sedatives or analgesics were placed into a subgroup. This subgroup of patients was compared with a cohort who received intravenous sedatives or analgesics for procedural sedation during a similar period the preceding year (January 2017 to June 2017). RESULTS: Of the 196 cases, 100% of the providers were comfortable using IN ketamine. The median overall provider satisfaction was 90 out of 100, the perception of patient comfort was 75 out of 100, and perceived patient comfort was maximized when using doses between 3 and 5 mg/kg. There were 15 (7.7%) patients who experienced ketamine treatment failure. Overall, the rate of adverse events was 6%, but were considered minor [nausea (n = 3; 1.5%), dizziness (n = 2; 1%), and drowsiness (n = 2; 1%)]. No patients required respiratory support or intubation. The mean LOS was 237.9 minutes, compared with those who underwent procedural sedation with an LOS of 332.4 minutes (P < 0.001). CONCLUSIONS: This study demonstrates that IN ketamine was able to provide safe and successful analgesia and anxiolysis in pediatric patients in an ED setting. In addition, providers expressed a high degree of satisfaction with using IN ketamine (90 out of 100) in addition to a high degree of patient comfort during the procedure (75 out of 100). Intranasal ketamine provides an alternative to intravenous medication normally requiring more resource-intensive monitoring. Procedural sedations are resource and time intensive activities that increase ED LOS. Intranasal ketamine used for anxiolysis and analgesia offers the benefits of freeing up resources of staff and monitoring while enhancing overall throughput through a pediatric ED.

Compliance and Related Outcomes of Prophylactic Antibiotics in Traumatic Open Fractures.

Purpose: Prophylactic antibiotic therapy is a standard of care for patients who present with open fractures due to the risk of infectious complications. This study was conducted to characterize the use of initial prophylactic antibiotic use in open fractures, guideline compliance, and its impact on care. Methods: Retrospective chart review of adult patients presenting with an open fracture to a Level 1 Trauma Center Emergency Department over a 12-month period was conducted. Results: Of the 202 patients meeting inclusion criteria, overall compliance with guideline recommendations for antibiotic prophylaxis was found to be 33.2%. The duration of prophylactic therapy was significantly longer in the noncompliant group and among those who received a secondary antibiotic (P < .05 for both comparisons). The duration of therapy was found to be significantly longer in those patients who developed an infection (P < .001). Those who developed an infection had a longer hospital length of stay (LOS) (P < .001) and intensive care unit LOS (P = .002). In addition, those who developed an infection had significantly more surgeries (P < .001) and received more red blood cell transfusions (P < .001). Correlation analysis confirmed a significant association between infection and duration of antibiotic prophylaxis (P = .02), number of surgeries (P < .0001), and number of transfusions (P < .0001). Conclusion: Guideline compliance was exceedingly low due to the extended duration of initial antibiotic therapy and did not appear to yield any clinical benefits. Infection was significantly associated with longer duration of initial prophylactic therapy and morbidity. Opportunities exist to elevate compliance with guidelines and to reevaluate prophylactic antimicrobial therapy in this setting.

Chomping at the Bit: A Descriptive Report on Pediatric Clenbuterol Ingestion.

INTRODUCTION: Clenbuterol hydrochloride is a selective beta-2 adrenergic agonist with uses in both humans and animals. Ingestions occurring within the United States are generally due to incidental ingestion of a veterinary product, use as a cutting agent for illicit substances, or illegal use for performance-enhancing purposes. CASE REPORT: A four-and-a-half year-old male presented approximately two-and-a-half hours after an accidental ingestion of an unknown quantity of clenbuterol. Initial laboratory results and electrocardiogram were remarkable for hyperglycemia, hypokalemia, and hypophosphatemia, with an electrocardiogram demonstrating sinus tachycardia. Heart rate ranged from 126 to 147 beats per minute while other vitals remained within normal limits. The patient was observed for 24 hours and discharged with normalized vital signs, laboratory results, and electrocardiogram. DISCUSSION: Clenbuterol hydrochloride is a beta-agonist with high potency, extended half-life, and bioavailability of 70% to 80%. Tachycardia occurs due to beta-1 receptor stimulation, as well as a homeostatic reflex to peripheral vasodilation. Hyperglycemia is not uncommon in exposures and intracellular shifting of potassium causes hypokalemia. Treatment is primarily supportive in nature, with hemodynamic management representing the primary focus of initial triage.

Evaluation of infection rates with narrow versus broad-spectrum antibiotic regimens in civilian gunshot open-fracture injury.

INTRODUCTION: Civilian gunshot open-fracture injuries portray a significant health burden to patients. Use of antibiotics is endorsed by guideline recommendations for the prevention of post-traumatic infections, however, antimicrobial selection and their associated outcomes remains unclear. Therefore, we sought to compare infectious and other clinical outcomes between three antimicrobial cohorts in patients with gunshot-related fractures requiring operative intervention. MATERIALS AND METHODS: Patients were identified by retrospectively querying the University of Kentucky Trauma Registry for gunshot wound victims. A narrow regimen, an expanded gram-negative regimen, and a regimen containing a fluoroquinolone antimicrobial were identified for comparison. The primary outcome was a composite of infections at or before 14 days of hospitalization. Secondary endpoints included hospital length of stay, incidence of multidrug resistant bacteria and methicillin-resistant Staphylococcus aureus colonization, number of drug-related adverse events, number of Clostridium difficile infections, and 30-day mortality. RESULTS: 252 patients were selected for inclusion: 126 in the narrow regimen, 49 in the expanded gram-negative regimen, and 77 in the fluoroquinolone-based regimen. There were no statistical differences in the primary endpoint of early infectious outcomes between groups (p = 0.1797). The expanded gram-negative regimen was associated with increased hospital length of stay, and increased incidence of multi-drug resistant bacteria and methicillin-resistant Staphylococcus aureus colonization. There were no statistically significant differences in any of the remaining secondary endpoints. CONCLUSION: In this study evaluating civilian gunshot trauma, broad spectrum antibiotic coverage was not associated with improvements in post-traumatic infections. A randomized trial is needed to confirm these results.

A Review of the Management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis represent a spectrum of severe cutaneous adverse reactions that carry the potential for severe, long-term adverse effects, including death. Although medications are most commonly implicated in the development of these diseases, other factors, including infection and genetics, play a role. Management is generally supportive in nature and includes maintenance of the patient's airway, breathing, and circulation. Special disease considerations include the use of skin barrier management, unique infection prevention measures, and systemic immunomodulatory therapies.

Variability in training, practice, and prioritization of services among emergency medicine pharmacists.

PURPOSE: The purpose of this survey-based research project is to identify factors, including prior training, institution demographics, and pharmacist prioritization of services that may impact variability in practice among emergency medicine (EM) pharmacists. METHODS: An electronic survey was available for 6 weeks. Participants were contacted through professional membership directories. Survey questions addressed EM pharmacist training and institution demographics. Pharmacists were asked to define the frequency with which they performed ASHP-identified best practice services. RESULTS: Responses were received by 208 pharmacists (response rate = 9.4%) who were primarily from academic (48.1%) or community (47.6%) emergency departments (EDs). Pharmacists working in an academic ED were more likely to have EM postgraduate year 2 training (27.8%) compared to a community ED (11.2%) (p = 0.0182). Pharmacists practicing in an academic emergency department (ED) reported participating in traumas, care for boarded patients, and performing scholarly activities more frequently (p < 0.01) and medication reconciliations less frequently (p < 0.01) than those in a community ED. Most EM pharmacists reported postgraduate year 1 training (45.7%) as compared to postgraduate year 2 EM (18.3%) or critical care (13.7%) pharmacy residency training. CONCLUSION: Institution and ED demographics as well as pharmacist level of training can affect the frequency of services provided in the ED setting.

Suspected Synthetic Cannabinomimetic Intoxication: Case Series and Review.

PURPOSE: The purpose of this work was to retrospectively review patient cases presenting to the University of Kentucky Chandler Medical Center (UKCMC) emergency department (ED) with symptoms of suspected synthetic cannabinomimetic (SC) intoxication. These drugs, currently undetected by standard urine drug screen tests, comprise a structurally diverse group of compounds designed to mimic the psychoactive effects of Δ9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive cannabinoid in marijuana. SUMMARY: Fourteen cases of suspected SC intoxication were identified between July 1, 2015, through September 30, 2015. The median patient age was 25.5 years (range: 13-45 years), and most (64%) patients were males. The most common psychoactive symptom was agitation (n = 6, 42.9%), while the most common physical symptoms were altered level of consciousness (n = 9, 64.3%) and mydriasis (n = 3, 21.4%). Most cases resolved without complication in 24 hours; 2 patients required hospitalization. CONCLUSION: Recent legislation has failed to curb the public health concerns emanating from SC misuse. Education about the risks of SC use along with additional regulation may be required to remove the false sense of safety that some individuals, especially adolescents and young adults, may associate with these compounds, which are often misconstrued as "herbal marijuana." Clinicians need to be prepared to identify and treat symptoms of SC intoxication as incidents of toxicity continue to rise.

Antiemetic Use in the Emergency Department.

Nausea and vomiting are 2 of the most common complaints of patients presenting to the emergency department (ED). In addition, antiemetics are the most commonly prescribed medications in the ED behind analgesics. Treating these conditions can be complex, especially as one considers that nausea and/or vomiting could be the primary presenting illness or simply a symptom of a more complex etiology. Although there is a wide variety of pharmacotherapeutic options in the armamentarium to treat these conditions, very few consensus recommendations exist to help guide the use of antiemetic agents in the ED, leading to wide variability in medication use. Contributing to these variations in practice is the extended spectrum of etiologies and potential physiological factors that contribute to the development of nausea or vomiting. A thorough understanding of the pharmacology and administration of these agents can help practitioners devise tailored antiemetic regimens based upon the underlying etiology.

Review of Intranasally Administered Medications for Use in the Emergency Department.

BACKGROUND: Intranasal (IN) medication delivery is a viable alternative to other routes of administration, including intravenous (IV) and intramuscular (IM) administration. The IN route bypasses the risk of needle-stick injuries and alleviates the emotional trauma that may arise from the insertion of an IV catheter. OBJECTIVE: This review aims to evaluate published literature on medications administered via the IN route that are applicable to practice in emergency medicine. DISCUSSION: The nasal mucosa is highly vascularized, and the olfactory tissues provide a direct conduit to the central nervous system, bypass first-pass metabolism, and lead to an onset of action similar to IV drug administration. This route of administration has also been shown to decrease delays in drug administration, which can have a profound impact in a variety of emergent scenarios, such as seizures, acutely agitated or combative patients, and trauma management. IN administration of midazolam, lorazepam, flumazenil, dexmedetomidine, ketamine, fentanyl, hydromorphone, butorphanol, naloxone, insulin, and haloperidol has been shown to be a safe, effective alternative to IM or IV administration. As the use of IN medications becomes a more common route of administration in the emergency department setting, and in prehospital and outpatient settings, it is increasingly important for providers to become more familiar with the nuances of this novel route of medication delivery. CONCLUSIONS: IN administration of the reviewed medications has been shown to be a safe and effective alternative to IM or IV administration. Use of IN is becoming more commonplace in the emergency department setting and in prehospital settings.

Chemotherapy in the Emergency Department? There Is a Role for That: Methotrexate for Ectopic Pregnancy.

Approximately 1.6% of all emergency department (ED) visits in the United States are for vaginal bleeding in early pregnancy, translating to around 500,000 ED visits per year. A potentially life-threatening condition, ectopic pregnancy occurs in 1.5%-2% of pregnancies. Many patients will require either surgical or pharmacological intervention following a positive diagnosis. With regard to pharmacological options, methotrexate, largely known for its use in the oncology arena, has emerged as the most effective nonsurgical option and the pharmacological agent of choice. However, this therapy is not without its own unique adverse event profile and patients should be adequately educated on the monitoring parameters of this pharmacotherapy.

Characterization and Management of Patients with Heroin versus Nonheroin Opioid Overdoses: Experience at an Academic Medical Center.

STUDY OBJECTIVES: To characterize the differences between patients who had heroin and nonheroin opioid overdoses and to determine whether there were any significant differences in their management with regard to the naloxone use. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: A total of 923 patients admitted to the medical center who were identified for overdose by heroin or other opiate-related narcotics between January 2010 and September 2015; 480 patients experienced a nonheroin opioid overdose event, and 443 patients experienced a heroin overdose event. MEASUREMENTS AND MAIN RESULTS: Patients presenting with heroin overdose tended to be younger and male, with higher rates of hepatitis C virus (HCV) infection compared with those presenting with nonheroin opioid overdose (p<0.05). Patients in the heroin group were also more likely to have a previous overdose event, history of injection drug use, and history of prescription opioid abuse compared with the nonheroin group (p<0.05). Those presenting with heroin overdose were more likely to receive naloxone in the prehospital setting (p<0.05) but were less likely to receive naloxone once admitted (p<0.05). Patients with nonheroin opioid overdoses required more continuous infusions of naloxone (p<0.05) and admission to the intensive care unit (p<0.05). Of all 923 patients, 178 (19.3%) had a repeat admission for any reason, and 70 (7.6%) were readmitted over the course of the study period for another overdose event with the same drug. The proportion of patients presenting with a heroin overdose steadily increased from 2010-2015; the number of patients presenting to the emergency department with nonheroin opioid overdoses steadily decreased. As rates of heroin overdose increased each year, the incidence of HCV infection increased dramatically. CONCLUSION: This study indicates that the incidence of heroin overdoses has significantly increased over the last several years, and the rates of HCV infection 4-fold since the start of the study period. Patients admitted for nonheroin opioid overdose were more likely to be admitted to the hospital and intensive care unit compared with those admitted for heroin overdose. The rise in overdose events only further illustrates a gap in our understanding of the cycle of addiction, drug abuse, and overdose events.

Treatment of Diabetic Ketoacidosis With Intravenous U-500 Insulin in a Patient With Rabson-Mendenhall Syndrome: A Case Report.

Rabson-Mendenhall syndrome is a rare genetic disorder resulting from mutations in the insulin receptor and is associated with high degrees of insulin resistance. These patients are prone to complications secondary to their hyperglycemia including diabetic ketoacidosis (DKA). We report the case of a 19-year-old male with Rabson-Mendenhall syndrome presenting with DKA who required doses of up to 500 U/h (10.6 U/kg/h) of insulin. The patient's insulin infusion was originally compounded with U-100 regular insulin, although to minimize volume, the product was compounded with U-500 insulin. The DKA eventually resolved requiring infusion rates ranging from 400 to 500 U/h. Although numerous opportunities for medication errors exist with the use of U-500 insulin, this case outlines the safe use of concentrated intravenous insulin when clinically indicated for patients requiring extremely high doses of insulin to control blood glucose.