Evaluation of Inhaled Alprostadil in Hospitalized Adult Patients.

BACKGROUND: Intermittent inhaled alprostadil (iPGE1) may be a viable alternative to inhaled nitric oxide or epoprostenol for management of right ventricular failure, pulmonary hypertension (pHTN) or acute respiratory distress syndrome (ARDS). However, limited evidence exists regarding iPGE1 use in adults, ideal dosing strategies, or optimal use cases. OBJECTIVE: To describe the clinical characteristics of patients receiving iPGE1 and identify specific sub-populations warranting further research. METHODS: This was a single-center, retrospective, descriptive analysis of inpatients who received at least one dose of iPGE1. The primary outcome was to describe patient characteristics and alprostadil dosing strategies. Secondary outcomes included changes in respiratory support requirements, hemodynamics, and inotropic/vasoactive use. Outcomes were stratified and compared based on primary therapeutic indication (cardiac or pulmonary). RESULTS: Fifty-four patients received iPGE1 40 (75%) for pulmonary (pHTN or ARDS) and 14 (25%) for cardiac indications. There was no difference between indications in the number of patients de-escalated from level of respiratory (53% vs 57%, P = 0.76), inotropic (70% vs 57%, P = 0.39), or vasopressor support (78% vs 57%, P = 0.17). Furthermore, there was no significant improvement in cardiopulmonary parameters at multiple time intervals after iPGE1 initiation. CONCLUSION AND RELEVANCE: This is the largest study to date on the use of intermittent iPGE1 in adults. Alprostadil was safely utilized in novel populations; however, efficacy as evaluated by clinical or surrogate endpoints could not be demonstrated and further investigation is needed to determine its potential and optimal place in therapy.

Updates in Hemodynamic Monitoring: A Review for Pharmacists.

Vital signs are regularly monitored in hospitalized patients. In the intensive care unit (ICU), traditional non-invasive blood pressure monitoring and telemetry may not provide enough information to determine the etiology of hemodynamic instability or guide intervention. Arterial catheters remain the gold-standard for continuous blood pressure monitoring and are commonly used in ICU patients. Pulmonary artery catheters and central venous catheters are beneficial in select patient populations and provide more advanced and specific information about a patient's hemodynamics. However, neither are benign and can increase risk of complications such as infection, arrhythmias, pneumothorax and vascular or valvular damage. In the past 10 years, the development of reliable non-invasive (NICOM), or minimally-invasive (MICOM), cardiac output monitoring devices has accelerated. The MICOM devices require an arterial catheter to obtain hemodynamic values, whereas NICOM devices do not require any arterial or venous access. These devices have emerged to be particularly useful in evaluating and managing patients with suspected mixed shock. As these devices become more prevalent, it is imperative that clinical pharmacists become familiar with interpreting this data as it may have a substantial impact on medication selection and optimization. This review will discuss the basics of NICOM and MICOM devices, limitations with these methods of monitoring, and clinical application for pharmacists.

Perioperative cangrelor in patients with recent percutaneous coronary intervention undergoing liver transplantation: A case series.

BACKGROUND: Management of dual antiplatelet therapy (DAPT) in the perioperative setting is challenging, particularly in complex patient populations, such as those with underlying coagulopathy and/or recent percutaneous coronary interventions. METHODS: In this case series, we describe the perioperative use of cangrelor bridge therapy in two patients undergoing liver transplantation after recent coronary drug-eluting stent placement. OUTCOMES: In both patient cases, cangrelor use as a P2Y12 bridge at a dose of 0.75 µg/kg/min was safe and effective. Both patients were successfully switched back to their oral DAPT regimen post-operatively without additive bleeding or thrombotic complications. CONCLUSION: The use of cangrelor as bridge therapy in high-risk perioperative liver transplant patients appears to be a viable option when DAPT is warranted.

Direct oral to parenteral anticoagulant transitions: Role of factor Xa inhibitor-specific anti-Xa concentrations.

OBJECTIVES: The increasing use of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of laboratory monitoring to enhance safety and effectiveness. Particularly, the use of FXaI-specific anti-Xa concentrations has gained traction and been advocated for several indications, but limited studies have explored the role of anti-Xa concentrations in guiding inpatient transitions from oral to parenteral anticoagulants. Therefore, additional data on such approaches are warranted to help balance bleeding and thrombotic risks in the higher acuity inpatient setting. This study sought to compare two strategies for oral-to-parenteral anticoagulant transitions: FXaI anti-Xa concentration-guided versus standard of care (i.e., per-package insert). STUDY DESIGN: This was an observational, single-center, retrospective cohort study conducted from May 2016 to May 2021. Hospitalized patients converted from an oral FXaI (apixaban or rivaroxaban) to therapeutic parenteral anticoagulation with or without FXaI anti-Xa concentration guidance were reviewed. The primary outcome of major bleeding, according to the International Society on Thrombosis and Hemostasis criteria, was compared between groups. Cox proportional hazard modeling was used to evaluate patient characteristics associated with major bleeding events. RESULTS: A total of 845 patients (388 in the concentration-guided group and 457 in the non-concentration-guided group) met the inclusion criteria. Major bleeding was significantly lower in the concentration-guided versus the non-concentration-guided group (2.2% vs. 11.3%; p < 0.001, respectively). There were no differences between the groups in thromboembolic complications (1.8% concentration guided vs. 1.5% non-concentration guided; p = 0.72) despite a significantly longer time from last oral FXaI dose to parenteral anticoagulant initiation in the concentration-guided group (27.9 h vs. 15.1 h; p < 0.01). The concentration-guided group had an 80% lower risk of major bleeding compared with the non-concentration-guided group (adjusted hazard ratio [HR] 0.20, 95% confidence interval [CI] 0.10-0.39; p < 0.01). CONCLUSIONS: This analysis suggests using FXaI anti-Xa concentrations to guide the transition from oral to parenteral anticoagulants may be beneficial in reducing major bleeds in select patient populations.

Direct Oral to Parenteral Anticoagulants: Strategies for Inpatient Transition.

The primary objective of this study was to describe the impact on bleeding rates of 2 different strategies for transitioning from a direct oral anticoagulant (DOAC) to a parenteral anticoagulant: a delayed, clinically driven strategy versus the standard per-package-insert strategy. This was a single-center descriptive cohort study conducted at a large academic medical center. Included patients were 18 years or older, admitted as an inpatient, and had received at least 1 dose of a DOAC prior to initiation of therapeutic parenteral anticoagulation. The primary end point was the incidence of major bleeds on the transition from a DOAC to a parenteral anticoagulant via a standard versus an intentionally delayed strategy. The secondary outcomes evaluated renal function, reason for delay, DOAC anti-factor Xa concentration, international normalized ratio values, blood product administration, and thrombotic complications. A total of 300 patients were included. The primary end point of bleeding was higher in the delayed group than the standard group, 25% and 12%, respectively (odds ratio, 0.39; P < .05). In both groups, patients who bled had a higher severity of illness, a greater incidence of acute kidney injury, and, when available, higher median DOAC anti-factor Xa concentrations. Despite a more conservative approach, patients in the delayed group experienced more bleeding, most likely attributable to a higher severity of illness, which highlights emerging challenges of inpatient anticoagulation management. Further prospective studies analyzing DOAC pharmacodynamics and pharmacokinetics in acutely ill patients are warranted.