Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow® Assay.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Low-Dose Valganciclovir Prophylaxis Against Cytomegalovirus in Intermediate-Risk Liver and Dual-Abdominal Transplant Recipients.

BACKGROUND: Low-dose valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis post-transplant has been employed due to cost and safety. The incidence of CMV disease in CMV intermediate-risk liver recipients at 1-year after standard-dose prophylaxis is approximately 5%. However, there are limited data on outcomes after using a "true" low-dose VGC prophylaxis regimen in liver and dual-abdominal transplant recipients as VGC was not dose-adjusted in all patients with impaired renal function in prior studies. OBJECTIVE: The objective was to assess the incidence of CMV associated with low-dose VGC prophylaxis in CMV intermediate-risk liver, simultaneous pancreas-kidney (SPK), and simultaneous liver-kidney (SLK) recipients with creatinine clearance (CrCl) >60 mL/min. METHODS: This was a retrospective review of CMV intermediate-risk liver, SPK, and SLK recipients with CrCl >60 mL/min transplanted January 2018 to June 2022 who received VGC 450 mg daily for prophylaxis. The primary outcome was incidence of CMV infection 6-months post-transplant. RESULTS: Ninety-nine transplant recipients were included (79 liver, 11 SPK, 9 SLK). The primary outcome occurred in 13% of patients (liver 10%, SPK 36%, SLK 10%), including 1 case of CMV disease and 3 breakthrough infections. In addition, 6 patients experienced CMV infection between 6-months and 1-year. Recurrence occurred in 3 patients. There was no evidence of CMV resistance. Thirty patients experienced neutropenia within 1-year, 32 were prescribed granulocyte-colony stimulating factors, and 5 experienced thrombocytopenia. Two patients died due to graft-vs-host disease. CONCLUSION AND RELEVANCE: Low-dose VGC prophylaxis led to comparable CMV infection rates at 6-months in CMV intermediate-risk liver and SLK recipients. However, as SPK recipients displayed higher rates of CMV infection, low-dose VGC should be avoided in this population.

A Comparison of Prothrombin Complex Concentrate and Recombinant Activated Factor VII for the Management of Bleeding With Cardiac Surgery.

Bleeding following cardiac surgery that warrants transfusion of blood products is associated with significant complications, including increased mortality at 1 year following surgery. Factor concentrates, such as prothrombin complex concentrate (PCC), or recombinant activated factor VII (rFVIIa) have been used off-label for bleeding in cardiac surgery that is refractory to conventional therapy. The objective of this retrospective study is to assess the hemostatic effectiveness of 4-factor PCC or rFVIIa for bleeding after a broad range of cardiac surgeries. Patients were included if they were at least 18 years of age and had undergone cardiac surgery with bleeding requiring intervention with 4-factor PCC or rFVIIa. There were no differences observed in the number of packed red blood cells (4-factor PCC: 2 units vs. rFVIIa: 2 units), fresh frozen plasma (0 units vs. 1 unit) or platelet (2 units vs. 2 units) transfusions following the administration of 4-factor PCC or rFVIIa. The patients in the rFVIIa group, required more cryoprecipitate than those in the 4-factor PCC group (4-factor PCC: 2 units (range 0-6) vs. rFVIIa: 2 units (range 0-8), p = 0.03). There were no differences in secondary outcomes of chest tube output at 2, 6, 12 and 24 hours, nor was there a difference in reexploration rates or the median length of stay in the intensive care unit. Thromboembolic complications at 30 days were similar between the two groups (4-factor PCC: 13% vs. rFVIIa 26%, p = 0.08). The total median dose requirement for 4-factor PCC was 1000 units (15 units/kg) and 2 mg (20 mcg/kg) for rFVIIa. The results demonstrate feasibility of utilizing the minimum amount of drug in order to achieve a desired effect. Both 4-factor PCC and rFVIIa appear to be safe and effective options for the management of bleeding associated with cardiac surgery.

Real world prescribing practices of apixaban or rivaroxaban lead-in doses for the treatment of venous thromboembolism in hospitalized patients.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Clinical Use of Cangrelor After Percutaneous Coronary Intervention in Patients Requiring Mechanical Circulatory Support.

BACKGROUND: Patients with cardiogenic shock after percutaneous coronary intervention (PCI) may require mechanical circulatory support (MCS). The combination of dual antiplatelet therapy with cangrelor and continuous anticoagulation required for MCS may increase the risk of bleeding. OBJECTIVE: The objective of the study is to describe the complications and outcomes of patients who received cangrelor during MCS following PCI. METHODS: This is a single-center, retrospective, observational case series of 17 patients who received cangrelor while on MCS from June 2017 to September 2019. RESULTS: In a case series of 17 patients, 8 patients (47%) were supported with an Impella device and 4 patients (24%) with venoarterial (VA) extracorporeal membrane oxygenation (ECMO); 5 required (29%) concomitant VA ECMO and Impella support in the setting of cardiogenic shock. All patients received triple antithrombotic therapy with aspirin, heparin, and cangrelor. Cangrelor was commonly initiated at a median dose of 0.75 (range 0.5-4) µg/kg/min. Cangrelor dose adjustments included changes in increments up to 0.25 µg/kg/min with review of P2Y12 levels. A total of 10 patients (59%) experienced a bleeding event, most commonly located at the peripheral cannulation site (40%) and in the gastrointestinal tract (30%). Seven (70%) and 3 (30%) of the bleeding complications were classified as major and minor, respectively. No patient developed in-stent thrombosis during the hospitalization; 14 (82%) patients survived their MCS course. CONCLUSION AND RELEVANCE: This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

Clinical effects of intravenous to oral amiodarone transition strategies in critically ill adult patients.

WHAT IS KNOWN AND OBJECTIVE: There is limited guidance on how to transition critically ill patients from intravenous (IV) to oral (PO) amiodarone. The objective of this study was to assess the impact of IV and PO amiodarone overlap on short-term tachyarrhythmia recurrence and adverse hemodynamic outcomes in the intensive care unit. METHODS: This is a retrospective, single-center analysis of critically ill adults who were treated with IV amiodarone for a supraventricular arrhythmia with rapid ventricular rate (RVR) and transitioned to PO amiodarone while inpatient. Patients were excluded if rate control was not achieved prior to the PO transition. Receipt of concomitant IV and PO therapy for ≤2 hours was considered no overlap (NOV) and >2 hours was considered overlap (OV). Tachyarrhythmia recurrence and adverse hemodynamic events were compared between groups. RESULTS: A total of 90 patients (45 NOV, 45 OV) were included in the analysis. The median overlap duration was 0.1 (-1.3 to 1.2) hours in the NOV arm and 4 (2.6-6.1) hours in the OV arm. Recurrence of RVR occurred in 9 (20%) patients in each arm (P = 1.0). The median time from IV discontinuation to return of tachyarrhythmia was 10.5 hours. There were no significant differences in amiodarone dosing, electrolyte abnormalities, volume status or concomitant cardiac medications at the time of IV to PO transition. Hypotension occurred in 13% and 20% (P = 0.369) and bradycardia in 9% and 13% (P = 0.502) of patients in the NOV and OV arms, respectively. WHAT IS NEW AND CONCLUSION: Providing IV and PO overlap of amiodarone for a median of 4 hours did not decrease the rate of early tachyarrhythmia recurrence. Future studies are warranted to evaluate the impact of alternative amiodarone dosing strategies on breakthrough tachyarrhythmia.

A Case Report of Cardiac Arrest After Intravenous Administration of Sulfur Hexafluoride (Lumason®) Ultrasound Enhancing Agent.

Ultrasound enhancing agents (UEAs) are medications that enable clear visualization of ultrasound images. While large studies have demonstrated the safety of these agents, case reports of life-threatening reactions temporally associated with their use have been published and reported to the Food and Drug Administration. Current literature describes the most serious adverse reactions due to UEAs to be allergic in nature; however, embolic phenomena may play a role as well. Here, we report a case of unexplained cardiac arrest following the administration of sulfur hexafluoride (Lumason®) in an adult inpatient undergoing echocardiography where resuscitative efforts were ultimately unsuccessful, and review possible mechanisms of cardiac arrest based on prior published literature.

Evaluation of Low-dose Buprenorphine Initiation With Buprenorphine Buccal Films in Hospitalized Patients: A Retrospective Cohort Study.

OBJECTIVE: Low-dose buprenorphine initiation (LDBI) strategies to transition patients from full opioid agonists to buprenorphine have previously been described using sublingual films, intravenous solution, transdermal patches, and, more recently, buccal films. The objective of this study was to describe the effectiveness of LDBI using novel titration schedules with buccal films. METHODS: This is a retrospective cohort study of hospitalized patients with opioid use disorder (OUD) or physiologic dependence to opioids who underwent LDBI with buprenorphine buccal films at NYU Langone Health. Two LDBI protocols were evaluated, including a short titration schedule over 4 days and a long schedule over 7 days. The primary outcomes of interest included LDBI completion rates and incidence of opioid withdrawal. RESULTS: Forty-two patients underwent 46 LDBIs at NYU Langone Health between October 2020 and April 2022. The cohort comprised patients with OUD (57%), chronic pain with OUD (33%), and chronic pain without OUD (10%). Indications for LDBI most commonly included co-occurring pain precluding discontinuation of full opioid agonists (72%), prior history of precipitated withdrawal (30%), and methadone use (23%). The overall completion rate of LDBI was 78%. Withdrawal was encountered in 33% of patients; however, only 2 patients required LDBI discontinuation as a result. On multivariate analysis, a diagnosis of OUD was independently associated with withdrawal during LDBI. CONCLUSIONS: Buprenorphine buccal films can successfully be used off-label to facilitate LDBI in the hospital setting. We present 4- and 7-day titration protocols, which were well-tolerated, and provide practical considerations for use.

Evaluation of the Safety of Slow IV Push Versus Slow IV Infusion Administration of 23.4% Sodium Chloride.

Background and Purpose: Increased intracranial pressure due to cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Currently, safety data is limited on slow IV push (IVP) administration. The purpose of this study was to evaluate the safety of IVP administration of 23.4% NaCl and determine the number of infusion-related adverse events (IRAEs) compared to slow IV infusion (SIV) administration. Methods: We performed a retrospective review of patients who received a dose of 23.4% NaCl at the (removed institution) from January 2015 to June 2020 as either SIV over 30 minutes or IVP over 2-5 minutes. Results: In total, 81 patients, 55 in the IVP group and 26 in the SIV group, were included in the analysis. There was a significantly faster time from order entry to dose completion (IVP 25 [13,58] vs SIV 73 [55,113] minutes, P < .001). There was no difference in IRAEs between the groups (IVP 17 [31%] vs SIV 6 [23%], P = .466). Hypotension was most common (IVP 13 [24%] vs SIV 5 [19%], P = .656) followed by bradycardia (IVP 6 [11%] vs SIV 1 [4%], P = .291). There were no extravasations reported. Conclusions: Overall, among a cohort of patients with cerebral edema, we found no difference in the incidence of IRAEs between SIV and IVP administration of 23.4% NaCl, and found a faster time to complete administration fssor the latter. In emergent scenarios where time may impact neurologic function, 23.4% NaCl administered IVP may be an alternative to SIV administration.

Impact of oral vancomycin treatment duration on rate of Clostridioides difficile recurrence in patients requiring concurrent systemic antibiotics.

BACKGROUND: There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics. OBJECTIVES: To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. METHODS: In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE). RESULTS: Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11-14) and 20 days (16-26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). CONCLUSIONS: Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Antithrombotic management for Impella® temporary ventricular assist devices: An analysis of an academic health-system experience.

The use of acute mechanical circulatory support (MCS) has increased over the last decade. For patients with left-ventricular failure, an Impella® (Abiomed, Danvers, MA) may be used to improve cardiac output. The purpose of this study is to describe Impella® anticoagulation patterns and evaluate the safety and effectiveness of our protocol. This is a retrospective review of all adult patients who required at least 24 h of Impella® support and received a heparin-based purge solution. In total, 109 patients were included in the final analysis. The most common indication for Impella® device insertion was cardiogenic shock (76%) with the remaining patients receiving a device for a high-risk procedures; typically coronary artery bypass grafting or percutaneous coronary intervention. A total of 9 thrombotic events occurred among 8 (7%) patients and 50 bleeding events occurred among 43 (39%) patients, with the most common classification being BARC 3a (60%). A univariate analysis revealed that patients were more likely to bleed if they were less than 65 years old, had an indication of cardiogenic shock for Impella®, inserted the device peripherally, were on dual antiplatelet therapy, or had an intra-aortic balloon pump prior to Impella® insertion, the latter of which was confirmed with a multivariate analysis (OR 2.5 [1.072-5.830]; p = 0.034). For those monitored by anti-Xa, the presence of two or more values greater than 0.40 IU/mL was a risk factor for bleeding (p = 0.037). Our study identifies risk factors for bleeding in patients receiving temporary MCS with an Impella®.

Comparison of Outcomes of Enoxaparin Bridge Therapy in HeartMate II versus HeartWare HVAD Recipients.

BACKGROUND: There is a lack of robust data evaluating outcomes of enoxaparin "bridge" therapy in left ventricular assist device (LVAD) patients. METHODS: We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as "bridge" therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of "bridge" episode. Major bleeding was defined by INTERMACS criteria. RESULTS: We evaluated 257 "bridge" episodes in 54 patients, 35 with a HM II device and 19 with an HVAD device that underwent 176 and 81 bridging episodes, respectively. The median INR prior to "bridge" was lower in the HM II group compared to the HVAD group (1.5 vs 1.7, P < .01), however, there was no difference in the median duration of "bridge" therapy (7 vs 7 days, P = .42). There were a total of 30 (12%) bleeding episodes, with the majority in the HM II group vs HVAD (26 [15%] vs 4 [5%], P = .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. CONCLUSION: We found the use of enoxaparin "bridge" therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.

COVID-19 pandemic preparedness: A practical guide from clinical pharmacists' perspective.

PURPOSE: To describe our hospital pharmacy department's preparation for an influx of critically ill patients during the coronavirus disease 2019 (COVID-19) pandemic and offer guidance on clinical pharmacy services preparedness for similar crisis situations. SUMMARY: Personnel within the department of pharmacy at a medical center at the US epicenter of the COVID-19 pandemic proactively prepared a staffing and pharmacotherapeutic action plan in anticipation of an expected surge in admissions of critically ill patients with COVID-19 and expansion of acute care and intensive care unit (ICU) capacity. Guidance documents focusing on supportive care and pharmacotherapeutic treatment options were developed. Repurposing of non-ICU-trained clinical pharmacotherapy specialists to work collaboratively with clinician teams in ICUs was quickly implemented; staff were prepared for these duties through use of shared tools to facilitate education and practice standardization. CONCLUSION: As challenges were encountered at the initial peak of the pandemic, interdisciplinary collaboration and teamwork was crucial to ensure that all patients were proactively assessed and that their respective pharmacotherapeutic regimens were optimized.

COVID-19 pandemic preparedness: A practical guide from an operational pharmacy perspective.

PURPOSE: To describe our medical center's pharmacy services preparedness process and offer guidance to assist other institutions in preparing for surges of critically ill patients such as those experienced during the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY: The leadership of a department of pharmacy at an urban medical center in the US epicenter of the COVID-19 pandemic proactively created a pharmacy action plan in anticipation of a surge in admissions of critically ill patients with COVID-19. It was essential to create guidance documents outlining workflow, provide comprehensive staff education, and repurpose non-intensive care unit (ICU)-trained clinical pharmacotherapy specialists to work in ICUs. Teamwork was crucial to ensure staff safety, develop complete scheduling, maintain adequate drug inventory and sterile compounding, optimize the electronic health record and automated dispensing cabinets to help ensure appropriate prescribing and effective management of medication supplies, and streamline the pharmacy workflow to ensure that all patients received pharmacotherapeutic regimens in a timely fashion. CONCLUSION: Each hospital should view the COVID-19 crisis as an opportunity to internally review and enhance workflow processes, initiatives that can continue even after the resolution of the COVID-19 pandemic.

Evaluation of Anti-Xa and Activated Partial Thromboplastin Time Monitoring of Heparin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Support.

The approach to monitoring anticoagulation in adult patients receiving heparin on extracorporeal membrane oxygenation (ECMO) support is controversial. The objective of this study was to compare the correlation between anti-Xa and activated partial thromboplastin time (aPTT) with heparin dose and to describe their association with clinical events in adult ECMO patients. We conducted a retrospective single-center study of 34 adult ECMO patients whose heparin was monitored by anti-Xa and/or aPTT. The heparin dose-to-assay correlation coefficient was 0.106 for aPTT and 0.414 for anti-Xa (p < 0.001). Major thrombotic and hemorrhagic events occurred in 14.7% and 26.5% of patients, respectively. The median anti-Xa in patients who experienced a major thrombotic event was 0.09 (0.06-0.25) IU/mL compared with 0.36 (0.26-0.44) IU/mL in patients who did not (p = 0.031), whereas the median aPTT did not differ between these groups. The maximum aPTT in patients who experienced a major bleed was 96.9 (76.0-200) seconds compared with 63.5 (44.4-98.6) seconds in patients who did not (p = 0.049), whereas the maximum anti-Xa did not differ between these groups. Monitoring both anti-Xa and aPTT may be warranted to safely provide understanding of pure heparin activity as well as underlying bleeding diatheses in adult ECMO patients.