Evaluation of the safety of inpatient empagliflozin in a real-world setting.

Background: Empagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor recommended by the American Diabetes Association for outpatient use. Support for its inpatient role is not well established due to possible safety concerns. Methods: This was a retrospective study at an academic medical center between January 1, 2021, and December 31, 2021, evaluating the safety and efficacy of empagliflozin compared to other oral antihyperglycemic agents. Patients with established heart failure with or without diabetes were included if they received at least one dose of oral antihyperglycemic agent with 48 hours of fingerstick blood glucose checks during the hospitalization. A total of 227 patients were included. The primary endpoint was a composite of adverse events including urinary tract infection, acute kidney injury, diabetic ketoacidosis, renal replacement therapy, and necrotizing fasciitis. Additional endpoints included daily insulin requirements, hypoglycemia, and hypotension. Results: Rates of composite adverse events were similar between the empagliflozin group and other oral antihyperglycemic agents (19.3% vs. 12.6% respectively, P = 0.17). There were no instances of renal replacement therapy, diabetic ketoacidosis, or necrotizing fasciitis. The secondary endpoint of basal insulin requirements showed no differences between the two groups. In the empagliflozin cohort, more patients experienced hypotension (23.4% vs. 7.8%; P < 0.01). Conclusion: This real-world study of empagliflozin use in the inpatient setting found no significant differences in safety endpoints between empagliflozin and other oral antihyperglycemic agents. Larger-scale studies need to be performed before the use of empagliflozin can be routinely recommended in the inpatient setting.

Analysis of the use of empiric antimicrobial prophylaxis for temporary cardiac devices at a large academic medical center.

INTRODUCTION: Varying rates of access site infections with temporary percutaneous cardiac devices have been reported in the literature. The purpose of this study is to determine the impact of a change in institutional practice in utilizing antimicrobial prophylaxis to prevent access site infections in patients with these devices. METHODS: This observational, pre-post implementation analysis evaluated the benefit of prophylactic antimicrobial therapy in adult patients with temporary percutaneous cardiac devices admitted to cardiac intensive care units. Patients in the pre-cohort received prophylactic antibiotics for the duration of device insertion. Patients in the post-cohort received a single dose of intravenous antibiotics for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella® 5.5 device placement, and no antimicrobial prophylaxis for all other devices placed. The primary endpoint was the incidence of definitive access site infection. Secondary endpoints included the incidence of Clostridium difficile infection and initiation of broad-spectrum antibiotics. RESULTS: Fifty patients in the pre-cohort and 45 patients in the post-cohort were evaluated. Devices included intra-aortic balloon pumps, VA-ECMO, Impella® CP and Impella® 5.5. The median duration of device insertion was four days. No significant difference in the primary outcome was seen between the two groups. A significant reduction in prophylactic antimicrobial utilization and total days of antimicrobial exposure was observed in the post-implementation cohort. CONCLUSION: Based on the results of our study, the implemented guideline reduces the utilization of antimicrobial prophylaxis in patients with temporary percutaneous cardiac devices and does not result in an increased rate of infections.

Apixaban and Rivaroxaban Anti-Xa Concentration Utilization in Clinical Practice.

ABSTRACT: Drug-specific anti-Xa concentrations can be used to assess the presence of drug effects; however, there is inadequate guidance for clinicians on the interpretation and clinical application of these results. The purpose of this study is to review patients' first apixaban and rivaroxaban anti-Xa concentrations to identify indications for monitoring and common therapeutic interventions made based on the results. In addition, we compared bleeding and thrombotic outcomes between the obesity group body mass index ≥40 kg/m 2 and the standard group body mass index 25-39.9 kg/m 2 . A retrospective analysis was conducted at a large academic medical center from January 1, 2020, to December 31, 2020. Primary outcomes were indications for anti-Xa concentrations and interventions on results. A total of 180 patients were included in the analysis, with 119 patients (66%) in the apixaban group and 61 patients (34%) in the rivaroxaban group. The most common indications for anti-Xa concentrations were extreme body weight (23%) and concern for bleeding (22%). About half of the anti-Xa concentrations resulted in therapy changes including holding for procedure, switching to heparin or enoxaparin, holding for an elevated anti-Xa concentration or concern for bleeding, adjusting direct-acting oral anticoagulant dose, or switching to an alternative oral anticoagulant. There were no differences in bleeding complications (5% [2] vs. 16% [14], P = 0.11) or thrombotic complications (8% [3] vs. 9% [8], P = 0.85) between the obesity group and the standard group. Despite the lack of validation of therapeutic ranges for anti-Xa concentrations, this study showed clinical situations where anti-Xa concentration monitoring can be of value.

Cardiovascular Pharmacology.

Pharmacologic therapy is an integral component in the management of most cardiovascular emergencies. This article reviews the pharmacotherapy involved in the treatment of acute coronary syndromes, acute heart failure, and various arrhythmias. The focus will be to provide practical pearls that can be applied at the bedside in the Emergency Department.

Safety and Efficacy of Periprocedural Bridging With Cangrelor Versus Eptifibatide.

ABSTRACT: Patients with percutaneous coronary interventions undergoing procedures often require interruptions in their dual antiplatelet therapy. Periprocedural bridging is considered for patients at high thrombotic risk using intravenous cangrelor, a reversible P2Y12 inhibitor with a short half-life, or eptifibatide, a glycoprotein IIb/IIIa inhibitor, with a slightly longer half-life but less costly alternative. This study aims to assess the safety and efficacy of cangrelor compared with eptifibatide when used in a periprocedural setting. The primary outcome of this retrospective cohort study was the incidence of bleeding events defined by the global use of strategies to open occluded coronary arteries criteria, and the secondary outcomes include the transfusion requirements, inpatient major cardiac adverse events, and cost savings per patient. A total of 75 patients were included who were bridged to procedures (cangrelor, n = 50; eptifibatide, n = 25). There were no significant differences in overall bleeding events defined by global use of strategies to open occluded coronary arteries criteria: mild bleeding [8% (n= 4) vs. 8% (n= 2); P = 0.68], moderate bleeding [28% (n = 14) vs. 48% (n = 12); P = 0.07), and severe bleeding [8% (n = 4) vs. 8% (n = 2); P = 0.25] between cangrelor and eptifibatide. The composite inpatient major cardiac adverse events were also similar between cangrelor and eptifibatide [10% (n = 10) vs. 8% (n = 8); P = 0.78]. The average cost savings per each cangrelor patient on the equivalent duration of eptifibatide was calculated out to be $5824 per patient. Cangrelor and eptifibatide were similar in terms of safety and efficacy when used as a bridge in patients with recent coronary stents, but considerable cost savings could be made if cangrelor was substituted for by eptifibatide in select patients. Further studies are needed to determine its applicability specifically in patients at high thrombotic and hemorrhagic risk.

Standard Sedation and Sedation With Isoflurane in Mechanically Ventilated Patients With Coronavirus Disease 2019.

OBJECTIVES: To describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane. DESIGN: This was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records. SETTING: ICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines. PATIENTS: Consecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five mechanically ventilated patients were included in the study, with a mean (sd) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation (sd) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean (sd) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time (sd, 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [sd, 1,346] vs 6678 [sd, 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [sd, 1,635] before vs 950 [sd, 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [sd, 30] before vs 23 [sd, 27] mg). CONCLUSIONS: In the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions.

Evaluation of direct thrombin inhibitors during a critical heparin shortage.

A recent heparin shortage related to an outbreak of African Swine Flu in China led to substantial increase in the use of direct thrombin inhibitors (DTI) as an alternative. We evaluated the safety and efficacy of DTIs by assessing the anticoagulation assays within the initial 48 h of therapy comparing before and during shortage. A retrospective evaluation of bivalirudin and argatroban was conducted at a single center before (May 24, 2018 through August 25, 2019) and during heparin shortage (August 26, 2019 through February 20, 2020). The primary outcome was time to first therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included the percentage of time in therapeutic aPTT range, in-hospital mortality, incidence of recurrent thrombosis, and hemorrhagic events. Of the 204 patients included in the study, 95 patients [bivalirudin (n = 35), argatroban (n = 60)] were included in the pre-shortage cohort and 109 patients [bivalirudin (n = 68), argatroban (n = 41)] were during shortage. No significant difference was observed in the time to first therapeutic aPTT pre- and during shortage (8.9 h ± 10.8 vs 8.8 h ± 10.2, P = 0.62). Compared to pre-shortage cohort, a greater percentage of time was spent in therapeutic aPTT range within the initial 48 h (32% (0-50) vs. 41.6% (0-63), P = 0.04) during shortage without statistically significant differences in the rates of in-hospital mortality, thrombosis, or bleeding. While the optimal DTI protocol is still be determined, the protocols presented in this study allowed for wide-spread utilization of DTIs during a critical heparin shortage without compromising patient safety and effectiveness, likely reflective of the enhancement of DTI protocols, clinician education, and multidisciplinary collaboration and guidance from pharmacy and hematology.