Faculty Bibliography

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.

Background: Fondaparinux is FDA-approved for prophylaxis of venous thromboembolism (VTE) in patients undergoing surgery as well as for the treatment of acute deep vein thrombosis and pulmonary embolism. Off-label, fondaparinux is used as an alternative to argatroban in the treatment of suspected or confirmed heparin-induced thrombocytopenia (HIT). The Antithrombotic/Hemostatic Stewardship Committee at NYU Langone Health (NYULH) provides guidance for the safe and effective use of fondaparinux, while assuring that an evidenced-based and cost-effective approach for utilization is maintained.
Aim(s): To evaluate the utilization of fondaparinux at NYULH and to assess guideline adherence, efficacy, safety, and cost avoidance.
Method(s): This was a retrospective review of adult patients who received fondaparinux between November 2016 and June 2019 at NYULH. The primary outcome was assessment of fondaparinux utilization based on the dosing guideline. Secondary outcomes included tolerability, safety, and cost-avoidance.
Result(s): Ninety-eight patients received fondaparinux, with the most frequent indications being suspected HIT (44%), VTE prophylaxis (23%), and continuation of home therapy (14%). Based on the NYULH fondaparinux dosing guideline, 97 (99%) patients were dosed appropriately. One patient (1%) received fondaparinux while on hemodialysis. Thromboembolic events occurred in 3 (3%) patients, major bleeding occurred in 4 (4%) patients and clinically relevant non-major bleeding occurred in 2 (2%) patients. In the 52 patients with suspected or confirmed HIT, the cost-avoidance of utilizing fondaparinux instead of argatroban was approximately $100,000.
Conclusion(s): The majority of fondaparinux utilization at NYULH is for suspected HIT, and dosing guidelines were followed in most cases. A low thromboembolic event rate with the use of fondaparinux was observed. The major and clinically relevant non-major bleeds experienced in six patients may be attributed to these patients' baseline high bleeding risk. Fondaparinux was a cost-effective alternative to argatroban in patients with suspected or confirmed HIT in this patient population. (Table Presented)

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 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 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.

INTRODUCTION/BACKGROUND:Hypoglycemia is a common adverse effect when intravenous (IV) insulin is administered for hyperkalemia. A prolonged infusion of dextrose 10% (D10) may mitigate hypoglycemia compared to dextrose 50% (D50) bolus. Our objective was to evaluate whether D10 infusion is a safe and effective alternative to D50 bolus for hypoglycemia prevention in hyperkalemic patients receiving IV insulin. METHODS: > 5.5) and received IV insulin and D10 infusion or D50 bolus within 3 h. The primary endpoint was incidence of hypoglycemia, defined as blood glucose (BG) ≤ 70 mg/dL, in the 24 h following IV insulin administration for hyperkalemia. RESULTS:A total of 134 patients were included; 72 in the D50 group and 62 in the D10 group. There was no difference in incidence of hypoglycemia between the D50 and D10 groups (16 [22%] vs. 16 [26%], p = 0.77). Symptomatic hypoglycemia, severe hypoglycemia, and hyperglycemia rates in the D50 and D10 groups were [5 (7%) vs. 2 (3%), p = 0.45], [5 (7%) vs. 1 (2%), p = 0.22], and [34 (47%) vs. 23 (37%), p = 0.31] respectively. Low initial BG was a predictor for developing hypoglycemia. CONCLUSIONS:In our study, D10 infusions appeared to be at least as effective as D50 bolus in preventing hypoglycemia in hyperkalemic patients receiving IV insulin. In context of ongoing D50 injection shortages, D10 infusions should be a therapeutic strategy in this patient population.

BACKGROUND/UNASSIGNED:Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS/UNASSIGNED:We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS/UNASSIGNED: = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION/UNASSIGNED:Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts. The projected cost for andexanet (based on dose and insurance) and % reimbursement/patient was compared to the actual cost of 4F-PCC. Hemostasis at 24 h (excellent/good vs. poor) and 30-day thrombotic complications were assessed. Of 126 patients who received 4F-PCC to reverse dFXaI, 46 (~ 10 per-year) met inclusion criteria. The median projected cost of andexanet was $22,120/patient, compared to $5670/patient for 4F-PCC (P < 0.001). The median hospital reimbursement was $11,492/hospitalization. The projected cost of andexanet alone would exceed the entire hospital reimbursement in 74% of patients by a median of $7604, while 4F-PCC cost exceeded the total hospital payments in 7% of patients in the same cohort (P < 0.001). Hemostasis was excellent/good in 72% of patients post-4F-PCC, compared to 82% in andexanet trials. Thromboembolic events occurred in 4% of patients following 4F-PCC versus 10% in andexanet trials. The projected cost of andexanet would exceed the national average hospital reimbursement/patient in nearly 75% of patients by over $7500/hospitalization. 4F-PCC was significantly less expensive, had lower rates of thrombosis, but also lower rates of good/excellent hemostasis compared to published data for andexanet.

WHAT IS KNOWN AND OBJECTIVE/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/CONCLUSIONS: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.

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.

Background:There is a paucity of data evaluating optimal dosing strategies of commonly utilized opioids and sedatives for patients on extracorporeal membrane oxygenation (ECMO) support where pharmacokinetic and pharmacodynamic variables of these administered agents are altered. Objective: To assess the daily dosing requirement of sedatives and analgesics for patients on venovenous (VV) and venoarterial (VA) ECMO after the initial ECMO cannulation period. Methods: We performed a retrospective, observational study of adult patients receiving sedation and analgesia while receiving ECMO support for at least 24 hours. Patients cannulated at an outside hospital more than 24 hours before transfer, those with a history of intravenous drug use or acute alcohol withdrawal, or those who died within 48 hours of ECMO initiation were excluded. Results: We evaluated 26 patients on ECMO, including 13 on VV and 13 on VA ECMO. The median dose of fentanyl was 140 µg/h, with the VV group requiring a higher dose compared with the VA group (167 vs 106 µg/h, P < 0.001). The median doses of dexmedetomidine and propofol were 0.7 µg/kg/h and 26 µg/kg/min, respectively, with no significant differences between groups (P = 0.38 and P = 0.24, respectively). The median daily doses of fentanyl, dexmedetomidine, and propofol did not significantly increase throughout the time on ECMO support. Conclusions and Relevance: We found that the overall opioid daily dosing requirements were lower than previously reported in the literature. Additionally, light sedation strategies with a target RASS of -1 to 0 are feasible in this patient population.