Bleeding Reversal With Antifibrinolytics or Cryoprecipitate Following Thrombolysis for Acute Ischemic Stroke: A Case Series.

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.

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.

Put It in the Air? Nebulized Opioids in the Emergency Department.

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.

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.

Occurrence of Hyperbilirubinemia in Neonates Given a Short-term Course of Ceftriaxone versus Cefotaxime for Sepsis.

OBJECTIVE: Ceftriaxone and cefotaxime are appealing options for the treatment of neonatal infections. Guidelines recommend cefotaxime as the cephalosporin of choice in neonates because of ceftriaxone's potential to cause hyperbilirubinemia. Unfortunately, due to cefotaxime discontinuation, providers must choose between alternative antibiotics. Clinicians at our institution adopted a protocol allowing for the utilization of cefepime and ceftriaxone for the management of neonatal sepsis. The objective of this study was to compare the incidence of hyperbilirubinemia between ceftriaxone and cefotaxime in the treatment of neonatal infections beyond the first 14 days of life. METHODS: This was a retrospective chart review of patients receiving ceftriaxone or cefotaxime for the treatment of neonatal infections. Patients were 15 to 30 days old at the time of antimicrobial administration and received at least 1 dose of ceftriaxone or cefotaxime during hospital admission. Patient characteristics and bilirubin levels were compared between ceftriaxone and cefotaxime. RESULTS: The analysis included 88 patients. There was no statistically significant difference between groups in age, gestational age, weight, and baseline total calcium and bilirubin levels. Normal baseline bilirubin levels increased to an abnormal level after antibiotic administration in 2 patients in the cefotaxime group and 1 patient in the ceftriaxone group. The median number of doses of cefotaxime and ceftriaxone were 3 and 2, respectively. CONCLUSION: Patients who received a short-term course of ceftriaxone did not have a higher likelihood of developing hyperbilirubinemia compared with those who received a short-term course of cefotaxime during their hospital stay.

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.

Comparison of Low- Versus High-Dose Four-Factor Prothrombin Complex Concentrate (4F-PCC) for Factor Xa Inhibitor-Associated Bleeding: A Retrospective Study.

BACKGROUND: Although andexanet alfa was recently approved as a specific reversal agent for apixaban and rivaroxaban, some providers still elect to administer 4-factor prothrombin complex concentrate (4F-PCC) instead, due to concerns surrounding efficacy, thrombotic risk, administration logistics, availability, and cost. Previous studies have described success with 4F-PCC doses ranging from 25 to 35 U/kg, with some guidelines recommending 50 U/kg. OBJECTIVES: The purpose of this study was to compare hemostasis between patients receiving low- (20-34 U/kg) versus high-dose (35-50 U/kg) 4F-PCC for the urgent reversal of apixaban and rivaroxaban. PATIENTS/METHODS: We performed a retrospective cohort study at a level one trauma center and comprehensive stroke center between January 2015 and December 2018. Main exclusion criteria included patients receiving less than 20 U/kg or if postreversal imaging were unavailable. Outcomes assessed included hemostasis for critical bleeding associated with apixaban or rivaroxaban and postoperative bleeding for reversal for emergent procedures. RESULTS: The low-dose strategy was administered to n = 57 (57.6%) patients at a mean dose of 26.6 U/kg. The high-dose strategy was used in n = 42 (42.4%) patients at a mean dose of 47.6 U/kg. There was no difference in hemostasis by dosing strategy (75.4% vs 78.6%, P = .715) or hospital mortality (19.3% vs 35.7%, P = .067). No difference was found for secondary end points, including thrombotic events (5.3% vs 2.4%, P = .635) and hospital length of stay (11.3 vs 12.5 days, P = .070). CONCLUSIONS: Our comparison addresses a gap in the literature surrounding optimal dosing and supports a similar efficacy profile between dosing low- versus high-dose treatment.

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.

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.

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.

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.

Update on Sepsis Treatment in the Emergency Department.

Sepsis continues to be a devastating, costly, and challenging syndrome to manage in emergency departments (ED) across the nation, and its impact seems to be only increasing. Recently, consensus recommendations have made some profound changes in the way we approach, classify, and treat sepsis. The ED serves as an important initial screening and intervention point for sepsis, and ED care can have a profound impact on overall morbidity and mortality. The provision of early fluid resuscitation, antimicrobial therapy, and vasopressor therapy, if appropriate, is essential in early care. The intent of this review was to compare and contrast changes associated with the management of sepsis in the ED, with particular focus on guideline recommendations for pharmacotherapeutic management.

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.

Delayed hematologic toxicity following rattlesnake envenomation unresponsive to crotalidae polyvalent antivenom.

North American rattlesnake envenomations are known to produce coagulopathies and thrombocytopenia. However, the occurrence of delayed hematologic toxicity (less than seven days after envenomation) is poorly characterized in the medical literature. While the recurrence of hematologic derangements has been documented following envenomation, it is usually in the absence of clinically significant bleeding. Although commonly recommended to treat delayed coagulopathies, the effectiveness of crotalidae polyvalent immune Fab ovine (CroFab®) in managing this condition remains in question and warrants further investigation and exploration. We describe the case of a 19-year-old male who presented following rattlesnake envenomation at a church service who was treated with antivenin for 48 h and discharged home only to return four days later with profound thrombocytopenia, coagulopathy, and clinically significant bleeding.

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.

Identification of Rate-Limiting Steps in the Provision of Thrombolytics for Acute Ischemic Stroke.

BACKGROUND: Tissue plasminogen activator (tPA) is the only pharmacotherapy shown to improve outcomes in acute ischemic stroke. The American Heart Association (AHA) recommends a door-to-needle (DTN) time of <60 minutes in at least 50% of patients presenting with acute ischemic stroke. OBJECTIVE: The purpose of this study was to analyze the possible barriers that may delay tPA administration within the emergency department (ED) of an academic medical center. METHODS: A retrospective chart review was conducted from February 2011 to October 2013. Patients were included if they were admitted through the ED with a diagnosis of acute ischemic stroke and received tPA. RESULTS: Of the 130 patients who met inclusion criteria, 43.1% received tPA in ≤60 minutes. Several factors were identified to be significantly different in those with a DTN time of >60 minutes-time to ED physician consultation, neurologist arrival, blood sample acquisition, and result time ( P < .05 for all comparisons). Correlation analysis demonstrated several independent variables associated with DTN time of ≤60 minutes-time from admission to ED physician consultation, receipt of computed tomography (CT) scan, blood sample acquisition, laboratory results, and neurology service arrival ( P < .05 for all comparisons). CONCLUSION: The findings from this study highlight the importance of prompt physician evaluation, direct transfer to the CT scanner, and a quick turnaround time on laboratory values. The development of protocols to ensure the rapid receipt of tPA therapy should focus on limiting any potential delay these steps may cause.

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.