Droxidopa for Vasopressor Weaning in Critically Ill Patients with Persistent Hypotension: A Multicenter, Retrospective, Single-Arm Observational Study.

BACKGROUND: Persistent vasopressor requirements are a common reason for delayed liberation from the intensive care unit (ICU) and adjunct oral agents are sometimes used to hasten time to vasopressor discontinuation. We sought to describe the use of droxidopa for vasopressor weaning in critically ill patients with prolonged hypotension. MATERIALS AND METHODS: This retrospective, single-arm, observational study included adult patients admitted to an ICU at two academic centers between 06/2016-07/2023 who received droxidopa for vasopressor weaning. Patients who received droxidopa prior to admission or for another indication were excluded. The primary outcome was time to vasopressor discontinuation, defined as when vasopressors were stopped and remained off for at least 24 h. Secondary outcomes included rates of tachycardia and hypotension post-initiation, norepinephrine equivalents pre- and post-initiation, concomitant oral agent use, and dosing. A subgroup analysis was conducted in patients receiving droxidopa via feeding tubes. RESULTS: A total of 30 patients met inclusion criteria. Median age was 62 years old, 12 (40%) were female, and 73% were in a cardiac/cardiac surgical ICU. Patients were on vasopressors for a median of 16 days prior to droxidopa initiation. Median (IQR) time to vasopressor discontinuation was 70 h (23-192) and norepinephrine equivalents decreased immediately after initiation (0.08 vs 0.02 mcg/kg/min, p < 0.001). MAP increased after droxidopa initiation (68.8 vs 66.5 mm Hg, p = 0.008) while heart rates were unchanged (86 vs 84 BPM, p = 0.37) after initiation. Patients who weaned from vasopressors within 72 h versus longer than 72 h after droxidopa initiation were more likely to be on lower norepinephrine equivalents prior to initiation (0.05 vs 0.12 mcg/kg/min, p = 0.013). Feeding tube administration did not impact time to vasopressor discontinuation (p = 0.93). CONCLUSIONS: Droxidopa may be considered an adjunct therapy for vasopressor weaning. Effects were similar when analyzing patients receiving droxidopa via feeding tube.

Evaluation of Bivalirudin During Adult Extracorporeal Membrane Oxygenation: A Retrospective Characterization of Dosing, Efficacy and Bleeding.

Objective: Although heparin is the current standard anticoagulant during venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO), factors including heparin-induced thrombocytopenia, heparin resistance and drug shortages necessitate alternative anticoagulants such as direct thrombin inhibitors. The aim was to characterize dosing, safety, and efficacy of bivalirudin during ECMO support. Methods: This retrospective single-center study included 24 adults on ECMO support who received ≥6 hours of bivalirudin. The primary endpoint was dose to first therapeutic activated partial thromboplastin time (aPTT). Secondary endpoints included evaluating dosing between ECMO modes, incidence of bleeding and thrombotic events, and time in therapeutic range (TTR). Results: The dose at time of first therapeutic aPTT was bivalirudin 0.05 [0.05-0.1] mg/kg/hour. Bivalirudin dosing requirements were lower in VAECMO compared to VV-ECMO patients and were not impacted by continuous venovenous hemofiltration. Time to therapeutic aPTT was 5.5 [2-13] hours for VA-ECMO and 4.5 [2-8.6] hours for VV-ECMO patients. During any mode of ECMO TTR was 58.3% [39.6-73.1]. Thrombotic events occurred in 3 (13%) patients and major bleeding occurred in 12 (50%) patients. Conclusions: Our findings demonstrated variable bivalirudin dosing requirements based on mode of ECMO and dosing modifications may not be required during CVVH. Factors including mode of ECMO, indication for bivalirudin and concomitant antiplatelet therapy may impact hematologic events. Application of this data can assist with developing a bivalirudin ECMO protocol which provides less variability in initial dosing and TTR.

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.

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.

A Weight- and Anti-Xa-Guided Enoxaparin Dosing Protocol for venous thromboembolism Prophylaxis in intensive care unit Trauma Patients.

BACKGROUND: Trauma patients are high risk for venous thromboembolism (VTE) and the optimal dosing strategy for prophylactic enoxaparin remains unknown. The purpose of this quality improvement project was to evaluate a weight-based and anti-Xa-guided enoxaparin dosing protocol in intensive care unit (ICU) trauma patients and to determine if the protocol led to reduced clinical VTE rates. MATERIALS AND METHODS: Adult trauma patients admitted for ≥ 48 hours to our surgical or neurosurgical ICUs who received ≥ 3 consecutive weight-based enoxaparin doses were eligible for inclusion into this pre-post implementation cohort study. Enoxaparin 30 mg every 12 hours was used for weight 50 to 100 kg and body mass index (BMI) < 40 kg/m2 and enoxaparin 40 mg every 12 hours for weight ≥ 100 kg or BMI ≥ 40 kg/m2. PRE cohort patients did not routinely receive anti-Xa level monitoring, while in the POST cohort, dosing was subsequently titrated to peak anti-Xa levels of 0.2 to 0.4 IU/mL. RESULTS: A total of 110 and 113 patients were included in the PRE and POST cohorts, respectively. Clinical VTE rates were similar between groups. In the POST cohort, 75% of patients achieved goal anti-Xa levels without dose titrations, while 12% of higher weight patients and 9.1% of lower weight patients required adjustment. When comparing weight quartiles, patients > 100 kg were more likely to have sub-prophylactic anti-Xa levels than those ≤ 69 kg. CONCLUSIONS: Our enoxaparin dosing protocol was safe and frequently achieved initial anti-Xa levels within goal, indicating that weight-based dosing alone may be sufficient. However, patients > 100 kg may benefit from anti-Xa monitoring as they are highest risk for sub-prophylactic levels despite higher initial enoxaparin dosing.