Empirical antimicrobial prescribing for pyelonephritis in patients discharged from 15 US Emergency Departments: an opportunity for improvement.

BACKGROUND: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing. OBJECTIVES: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics. METHODS: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs. All patients ≥18 years of age with a diagnosis of pyelonephritis between 2018 and 2020 were included. The primary endpoint was the proportion of patients who received initial inactive empirical antibiotic therapy and to identify predictive factors of inactive antibiotic therapy. RESULTS: Of the 3714 patients evaluated, 223 had culture-positive pyelonephritis. Median patient age was 50.1 years and patients were mostly female (78.3%). Overall, 40.4% of patients received an IV antibiotic, most commonly ceftriaxone (86.7%). The most frequently prescribed antibiotics were cefalexin (31.8%), ciprofloxacin (14.3%), cefdinir (13.5%) and trimethoprim/sulfamethoxazole (12.6%). Overall, 10.3% of patients received initial inactive therapy. After adjustment in a multivariable analysis, long-acting IV antibiotic was predictive of inactive therapy (OR 0.23, 95% CI 0.07-0.83). CONCLUSIONS: In our prospective, multicentre observational study, we found that only 40.4% of patients with pyelonephritis received empirical IV antibiotics in the ED, contributing to inactive therapy. Receipt of long-acting IV antibiotics was independently associated with a decreased rate of initial inactive therapy. This reinforces guideline recommendations to administer long-acting IV antibiotics empirically in the ED upon suspicion of pyelonephritis.

Implementation of Tenecteplase for Acute Ischemic Stroke Treatment.

INTRODUCTION: Acute ischemic stroke is a neurologic emergency, requiring rapid recognition and treatment with intravenous thrombolysis. Since the publication of the 2019 American Heart Association/American Stroke Association Guidelines that recommend tenecteplase as an alternative agent, several centers across the United States are transitioning from alteplase to tenecteplase as the agent of choice for thrombolysis in acute ischemic stroke. METHODS: Our health system transitioned to tenecteplase for the treatment of acute ischemic stroke in 2021 due to increasing evidence for efficacy and potential for improved door-to-needle time. Herein we describe our experience and provide guidance for other institutions to implement this change. CONCLUSION: Emergency nurses are vital to the care of acute ischemic stroke patients. There are several pharmacologic and logistical differences between alteplase and tenecteplase for this indication. This paper outlines these key differences.

Risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine.

OBJECTIVE: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. DESIGN: Retrospective cohort study. SETTING: A large multi-site health system with hospitals across the United States. PATIENTS: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001). CONCLUSION: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.

BACKGROUND: Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. METHODS: This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. RESULTS: Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. CONCLUSION: In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

Extracorporeal cardiopulmonary resuscitation: A primer for pharmacists.

PURPOSE: To describe the use of mechanical circulatory support in the setting of cardiac arrest and summarize pharmacists' role in extracorporeal cardiopulmonary resuscitation (ECPR). SUMMARY: ECPR is increasingly used to reduce morbidity and improve mortality after cardiac arrest. ECPR employs venoarterial ECMO, which provides full circulatory perfusion and gas exchange in both adult and pediatric patients in cardiac arrest. After the emergency medicine team identifies potential candidates for ECPR, the ECMO team is consulted. If deemed a candidate for ECPR by the ECMO team, the patient is cannulated during ongoing standard cardiopulmonary resuscitation. A multidisciplinary team of physicians, nurses, perfusionists, pharmacists, and support staff is needed for successful ECPR. Pharmacists play a vital role in advanced cardiac life support (ACLS) prior to cannulation. Pharmacists intervene to make pharmacotherapy recommendations during ACLS, prepare medications, and administer medications as allowed by institutional and state regulations. Pharmacists also provide pharmacotherapy support in the selection of anticoagulation agents, ongoing vasopressor administration during ECMO cannulation, and the optimization of medication selection in the peri-ECPR period. CONCLUSION: With the growing use of ECPR, pharmacists should be aware of their role in medication optimization during ECPR.

Safety and effectiveness of benzodiazepines and antipsychotics for agitation in older adults in the emergency department.

PURPOSE: To examine the safety and effectiveness of benzodiazepines (BZD) as compared to antipsychotics for the management of acute agitation in older adults in the emergency department (ED). BASIC PROCEDURES: Retrospective observational cohort study of 21 EDs across four states in the US, including adults ≥60 years old who received either BZD or antipsychotics for acute agitation in the ED and subsequently were admitted to the hospital. Safety was measured as presence of adverse events: respiratory depression, cardiovascular effects, extrapyramidal side effects, or a fall during hospitalization. Effectiveness was measured as indicators of treatment failure: need for additional medication, one-to-one observation, or physical restraints following initial medication administration. Proportions and odds ratios with 95% confidence intervals (CI) were calculated. Univariable and multivariable logistic regression were used to assess the association between potential risk factors and for efficacy and safety endpoints. MAIN FINDINGS: A total of 684 patients were included (63.9% received a BZD and 36.1% an antipsychotic). There was no difference in the incidence of adverse events between groups (20.6% vs 14.6%, difference 6.0%, 95% CI -0.2% to 11.8%), but there was a higher intubation rate in the BZD group (2.7% vs 0.4%, difference 2.3%). There were more treatment failures in the antipsychotic group for the composite primary efficacy endpoint (94.3% vs 87.6%, difference 6.7%, 95% CI 2.5% to 10.9%). This appears to have been driven by the need for 1:1 observation; sensitivity analysis excluding 1:1 observation in the composite outcome demonstrated no significant difference with a failure rate of 38.5% in the antipsychotic group and 35.2% in the benzodiazepine group. PRINCIPAL CONCLUSIONS: Overall there are high rates of treatment failure among agitated older adults receiving pharmacological treatment for agitation in the emergency department. The optimal selection of pharmacological treatment for agitation in older adults should be made considering patient-specific factors that could increase the risk of adverse effects or treatment failure.

The incidence of cardiovascular instability in patients receiving various vasopressor strategies for peri-intubation hypotension.

INTRODUCTION: Patients frequently experience hypotension in the peri-intubation period. This can be due to the underlying disease process, physiologic response to the intervention, or adverse effect from medications. With the heterogeneity in cause for hypotension, the duration can also be short or prolonged. Initiation of vasopressors for peri-intubation hypotension includes various strategies using continuous infusion norepinephrine (NE) or push-dose phenylephrine (PDPE) to obtain goal mean arterial pressure. There is a paucity of data describing cardiovascular stability outcomes in patients receiving vasopressors for peri-intubation hypotension. METHODS: This is a retrospective cohort study including emergency department patients across three academic medical centers and smaller health system sites who received vasopressors for hypotension within 30 min of intubation. Patients were matched based on factors likely to influence vasopressor selection and were divided into groups if they received PDPE alone, continuous infusion NE alone, or PDPE followed by continuous infusion NE. The primary outcome was a composite of the incidence of hypotension (systolic blood pressure < 90 mmHg), bradycardia (HR < 60 beats per minute), and cardiac arrest within 2 h following initiation of vasopressors. RESULTS: Screening occurred for 2518 patients, with 105 patients undergoing matching. Mean time to vasopressor initiation was 10 min following intubation. The composite primary outcome was not statistically different between groups and occurred 88.6%, 80.0%, and 88.6% in the NE, PDPE, and PDPE+NE groups, respectively. A subgroup analysis of patients with an ED diagnosis of sepsis or septic shock were more likely to receive PDPE before starting continuous infusion NE (41.3% vs. 27.1%, p = 0.075) and more frequently experienced the primary composite outcome (p = 0.045) but was not correlated with vasopressor strategy (p = 0.55). DISCUSSION: Cardiovascular instability following vasopressor initiation for peri-intubation hypotension was no different depending on the selected vasopressor strategy. This held true in patients with a sepsis or septic shock diagnosis. Selection of vasopressors should continue to include patient specific factors and product availability.

High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.

BACKGROUND: Uropathogen resistance, fluoroquinolone-resistance (FQR), and extended spectrum beta-lactamase (ESBL), has been observed to be emerging worldwide with prevalences above recommended thresholds for routine empirical treatment. The primary aim of our study was to determine the prevalence of FQR from a geographically diverse sample of United States emergency departments (EDs). METHODS: We conducted a multi-center, observational cohort study using a network of 15 geographically diverse US EDs. All patients ≥18 years of age with the primary or secondary diagnosis of urinary tract infection (UTI) in the ED identified using International Classification of Diseases (ICD-10) diagnosis code of cystitis, pyelonephritis, or UTI from 2018 to 2020 were included. We calculated descriptive statistics for uropathogens and susceptibilities. Logistic regression analysis was used to identify antimicrobial resistance risk factors associated with FQR Escherichia coli. RESULTS: Among 3779 patients who met inclusion criteria, median age was 62.9 years (interquartile range [IQR]: 41-77.6) and 76.3% were female. The most common diagnoses were complicated (41.2%) and uncomplicated cystitis (40.3%). E. coli was the most common pathogen (63.2%), followed by Klebsiella pneumoniae (13.2%) and Enterococcus species (5.8%). Across all sites, overall E. coli FQ-resistance prevalence was 22.1%, ranging from 10.5 to 29.7% by site. The prevalence of ESBL-producing uropathogen was 7.4%, ranging from 3.6% to 11.6% by site. Previous IV or oral antimicrobial use in the past 90-days and history of a multi-drug resistant pathogen were associated with FQ-resistant E. coli (odds ratio [OR] 2.68, 95% confidence interval [CI]: 2.04-3.51, and OR 6.93, 95% CI: 4.95-9.70, respectively). Of the patients who had FQ-resistant E. coli or an ESBL-producing uropathogen isolated, 116 (37.1%) and 61 (36.7%) did not have any documented risk factors for resistance. CONCLUSION: FQ-resistant E. coli is widely prevalent across US sites highlighting the need for ongoing monitoring of antimicrobial resistance and, at some locations, modification of empirical treatments.

Description of telepharmacy services by emergency medicine pharmacists.

PURPOSE: Utilization of telemedicine and telepharmacy services has become increasingly popular, as specifically noted during the coronavirus disease 2019 (COVID-19) pandemic. This article describes the implementation of and services provided by emergency medicine pharmacists (EMPs) as part of a telemedicine team in the emergency department (ED). SUMMARY: This report describes the telemedicine and telepharmacy services provided to EDs in the Mayo Clinic Health System from the Mayo Clinic Rochester ED. Telepharmacy services provided by EMPs started in 2018. EMPs cover telepharmacy calls as part of their shift within the ED in Rochester. Recommendations and interventions are documented in the electronic medical record. A retrospective review evaluated interventions provided from November 18, 2018, through November 10, 2020. Baseline patient demographics, as well as the type and number of interventions provided by EMPs, hospital site, and time spent on the interventions, were collected. Telepharmacy consults could include multiple interventions and be classified as more than one type of intervention. During this time period, 24 pharmacists worked in the ED and were able to provide telepharmacy services. There were 279 consults included in this study, with 435 interventions. Most of the calls came from critical access hospitals (48.7%). The most common types of interventions documented were medication selection and dosing (n = 238), antimicrobials (n = 141), monitoring and follow-up (n = 65), discharge (n = 56), drug information (n = 55), and allergy review (n = 50). CONCLUSION: Telepharmacy services can provide increased access to emergency medicine specialty pharmacists in areas that would not otherwise have these services.

Comparison of Intravenous Antihypertensives on Blood Pressure Control in Acute Neurovascular Emergencies: A Systematic Review.

BACKGROUND: Acute blood pressure (BP) management in neurologic patients is paramount. Different neurologic emergencies dictate various BP goals. There remains a lack of literature determining the optimal BP regimen regarding safety and efficacy. The objective of this study was to identify which intravenous antihypertensive is the most effective and safest for acute BP management in neurologic emergencies. METHODS: Ovid EBM (Evidence Based Medicine) Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection were searched from inception to August 2020. Randomized controlled trials or comparative observational studies that evaluated clevidipine, nicardipine, labetalol, esmolol, or nitroprusside for acute neurologic emergencies were included. Outcomes of interest included mortality, functional outcome, BP variability, time to goal BP, time within goal BP, incidence of hypotension, and need for rescue antihypertensives. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to evaluate the degree of certainty in the evidence available. RESULTS: A total of 3878 titles and abstracts were screened, and 183 articles were selected for full-text review. Ten studies met the inclusion criteria; however, the significant heterogeneity and very low quality of studies precluded a meta-analysis. All studies included nicardipine. Five studies compared nicardipine with labetalol, three studies compared nicardipine with clevidipine, and two studies compared nicardipine with nitroprusside. Compared with labetalol, nicardipine appears to reach goal BP faster, have less BP variability, and need less rescue antihypertensives. Compared with clevidipine, nicardipine appears to reach goal BP goal slower. Lastly, nicardipine appears to be similar for BP-related outcomes when compared with nitroprusside; however, nitroprusside may be associated with increased mortality. The confidence in the evidence available for all the outcomes was deemed very low. CONCLUSIONS: Because of the very low quality of evidence, an optimal BP agent for the treatment of patients with neurologic emergencies was unable to be determined. Future randomized controlled trials are needed to compare the most promising agents.

Prospective real-time evaluation of the QTc interval variation after low-dose droperidol among emergency department patients.

OBJECTIVE: To assess the QTc interval variation after low-dose droperidol in a population of undifferentiated, stable, and non-agitated patients receiving droperidol in the emergency department. METHODS: Prospective cohort study of patients aged ≥12 years of age who received low-dose droperidol (≤ 2.5 mg) for indications other than acute behavioral disturbances. QTc intervals were monitored in real-time during pre-specified observation periods in the ED. Primary outcome was variation of QTc interval after droperidol administration, defined as the maximum delta (change) of QTc interval. Other outcomes included proportion of patients with a QTc ≥ 500 ms after droperidol, delta ≥ +60 ms, and incidence of clinical adverse events. Patients were monitored up to 30 min after IV bolus and up to 46 min after infusion. RESULTS: A total of 68 patients were included (mean age 42.1 years, 66.2% females). The median dose of droperidol was 1.875 mg (range 0.625 mg, 2.5 mg) and 94.1% received droperidol for headache management. Most patients received droperidol as a 2-min bolus (n = 41, 60.3%). The mean maximum delta of QTc interval after droperidol across all 68 patients was +29.9 ms (SD 15). A total of 12 patients (17.6%) experienced a QTc interval ≥ 500 ms during the observation period after droperidol, and 3 patients (4.4%) had a delta QTc ≥ +60 ms. There were no serious arrhythmias, such as TdP, or deaths among the 68 participants in this study (0/68). However, 13.2% (n = 9) had at least one non-serious adverse event including restlessness and/or anxiety. CONCLUSION: The QTc interval slightly increased after droperidol administration, but these prolongations were brief, mostly below 500 msec and did not lead to serious arrhythmias. The yield of continuous cardiac monitoring in patients receiving low doses of droperidol is likely low.

A Phase 2 Randomized Placebo-Controlled Adjuvant Trial of GI-4000, a Recombinant Yeast Expressing Mutated RAS Proteins in Patients with Resected Pancreas Cancer.

Purpose: GI-4000, a series of recombinant yeast expressing four different mutated RAS proteins, was evaluated in subjects with resected ras-mutated pancreas cancer. Methods: Subjects (n = 176) received GI-4000 or placebo plus gemcitabine. Subjects' tumors were genotyped to identify which matched GI-4000 product to administer. Immune responses were measured by interferon-γ (IFNγ) ELISpot assay and by regulatory T cell (Treg) frequencies on treatment. Pretreatment plasma was retrospectively analyzed by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-ToF) mass spectrometry for proteomic signatures predictive of GI-4000 responsiveness. Results: GI-4000 was well tolerated, with comparable safety findings between treatment groups. The GI-4000 group showed a similar pattern of median recurrence-free and overall survival (OS) compared with placebo. For the prospectively defined and stratified R1 resection subgroup, there was a trend in 1 year OS (72% vs. 56%), an improvement in OS (523.5 vs. 443.5 days [hazard ratio (HR) = 1.06 [confidence interval (CI): 0.53-2.13], p = 0.872), and increased frequency of immune responders (40% vs. 8%; p = 0.062) for GI-4000 versus placebo and a 159-day improvement in OS for R1 GI-4000 immune responders versus placebo (p = 0.810). For R0 resection subjects, no increases in IFNγ responses in GI-4000-treated subjects were observed. A higher frequency of R0/R1 subjects with a reduction in Tregs (CD4+/CD45RA+/Foxp3low) was observed in GI-4000-treated subjects versus placebo (p = 0.033). A proteomic signature was identified that predicted response to GI-4000/gemcitabine regardless of resection status. Conclusion: These results justify continued investigation of GI-4000 in studies stratified for likely responders or in combination with immune check-point inhibitors or other immunomodulators, which may provide optimal reactivation of antitumor immunity. ClinicalTrials.gov Number: NCT00300950.

Reintegrating droperidol into emergency medicine practice.

PURPOSE: After a long period of low utilization, droperidol has become easier to obtain in the US market. This comprehensive review discusses the safety, indications, clinical efficacy, and dosing of droperidol for use in the emergency department (ED) setting. SUMMARY: In 2001 the US Food and Drug Administration (FDA) mandated a boxed warning in the labeling of droperidol after reports of QT interval prolongation associated with droperidol use. Since that time, it has been difficult to access droperidol in the United States; as a result, many practicing clinicians lack experience in its clinical use. Multiple studies have been conducted to assess the clinical efficacy and safety of droperidol use in ED patients. Results consistently show the safety of droperidol and its clinical efficacy when used as an analgesic, antiemetic, and sedative. Now that droperidol is more widely available for use in the US market, pharmacists and prescribers need to reliably translate safety and efficacy data compiled since 2001 to help ensure appropriate and effective use of the medication. CONCLUSION: Droperidol is an effective and safe option for the treatment of acute agitation, migraine, nausea, and pain for patients in the ED setting. Healthcare professionals can adopt droperidol for use in clinical practice, and they should become familiar with how to dose and monitor droperidol for safe and effective use.

Safety of parenteral ketorolac use for analgesia in geriatric emergency department patients.

OBJECTIVE: To assess the safety of a single dose of parenteral ketorolac for analgesia management in geriatric emergency department (ED) patients. METHODS: This was a retrospective study of all administrations of parenteral ketorolac to adults ≥65 years of age and matched controls. The primary outcome was the occurrence of any of the following adverse events within 30 days of the ED visit: gastrointestinal bleeding, intracranial bleeding, acute decompensated heart failure, acute coronary syndrome, dialysis, transfusion, and death. The secondary outcome was the occurrence of an increase in serum creatinine of ≥1.5 times baseline within 7 and 30 days of the ED visit. RESULTS: There were 480 patients included in the final analysis, of which 120 received ketorolac (3: 1 matching). The primary outcome occurred in 14 of 360 patients who did not receive ketorolac and 2 of 120 ketorolac patients (3.9% vs 1.7%, p = 0.38; OR 2.39, 95% CI 0.54-10.66). There was no occurrence of dialysis or death in either group. The secondary outcome occurred in 1 of 13 and 1 of 23 ketorolac patients with both a baseline serum creatinine and a measure within 7 and 30 days, respectively, but did not occur in patients who did not receive ketorolac (7 days: 7.7% vs 0.0%, p = 0.29; 30 days: 4.4% vs 0.0%, p = 0.22). CONCLUSION: The use of single doses of parenteral ketorolac for analgesia management was not associated with an increased incidence of adverse cardiovascular, gastrointestinal, or renal adverse outcomes in a select group of older adults.

Effectiveness and safety of droperidol in a United States emergency department.

BACKGROUND: Droperidol is a dopamine receptor antagonist that functions as an analgesic, sedative, and antiemetic. In 2001, the U.S. Food and Drug Administration required a black box warning in response to case reports of QT prolongation and potential fatal arrhythmias. The aim of this study was to evaluate the effectiveness and safety of droperidol in patients presenting to a United States Emergency Department (ED). METHODS: Observational cohort study of all droperidol administrations from 1/1/2012 through 4/19/2018 at an academic ED. The primary endpoint was mortality within 24 h of droperidol administration. Secondary endpoint included use of rescue analgesics. RESULTS: A total of 6,881 visits by 5,784 patients received droperidol of whom 6,353 visits authorized use of their records for research, including 5.4% administrations in children and 8.2% in older adults (≥65). Droperidol was used as an analgesic for pain (N = 1,387, 21.8%) and headache (N = 3,622, 57.0%), as a sedative (N = 550, 8.7%), and as an antiemetic (N = 794, 12.5%). No deaths secondary to droperidol administration were recorded within 24 h. Need for rescue analgesia occurred in 5.2% of patients with headache (N = 188) and 7.4% of patients with pain (N = 102); 1.1% of patients with headache received rescue opioids (N = 38) after droperidol, as did 5.4% of patients with pain other than headache (N = 75). No patients had fatal arrhythmias. Akathisia occurred in 2.9%. CONCLUSION: No fatalities were seen among this large cohort of patients who received droperidol in the ED. Our findings suggest droperidol's effectiveness and safety when used as an analgesic, antiemetic and/or sedative.

Ethylene glycol and methanol ingestion cared for by tele-emergency pharmacy and tele-emergency medicine.

We believe this is the first documented case of a critically ill patient managed by telepharmacy in a remote, rural critical access hospital. We outline the case and the benefits of telepharmacy in under-resourced, rural critical access emergency departments.

Phase II study of the GI-4000 KRAS vaccine after curative therapy in patients with stage I-III lung adenocarcinoma harboring a KRAS G12C, G12D, or G12V mutation.

INTRODUCTION: Patients with early-stage lung cancer have a high risk of recurrence despite multimodality therapy. KRAS-mutant lung adenocarcinomas are the largest genetically defined subgroup, representing 25% of patients. GI-4000 is a heat-killed recombinant Saccharomyces cerevisiae yeast-derived vaccine expressing mutant KRAS proteins. The present phase II study assessed the feasibility, immunogenicity, and safety of the GI-4000 vaccine in patients with early-stage, KRAS-mutant lung cancer. MATERIALS AND METHODS: Patients with stage I-III KRAS-mutant lung cancer who completed curative therapy were enrolled. The patients received the genotype matched GI-4000 vaccine for ≤ 3 years or until intolerance, disease recurrence, or death. The KRAS antigen T-cell response was assessed using the interferon-gamma enzyme-linked immunospot assay in peripheral blood mononuclear cells. The study was powered to detect an immune response in ≥ 25% of patients. RESULTS: A total of 24 patients were enrolled over 28 months. No vaccine-related serious adverse events occurred. One patient withdrew consent because of pain at the injection site. The study met its primary endpoint, with 50% of patients developing an immune response to mutant KRAS. The median number of vaccinations received was 15 (range, 1-19). Ten patients experienced disease recurrence, and 6 died. Compared with the genotypically matched historical controls, the recurrence rates were equivalent but overall survival showed a favorable trend. CONCLUSION: GI-4000 was well tolerated and immunogenic when used as consolidation therapy in patients with stage I-III KRAS-mutant lung cancer. The patterns of recurrence and death observed in the present study can be used to design a randomized study of GI-4000 with overall survival as the primary endpoint.