Faculty Bibliography

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.

INTRODUCTION: Increased intracranial pressure (ICP) in the setting of cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Recently, our institution updated the 23.4% NaCl prescriber order entry to default to IV push (IVP) over 2 or 5 minutes rather than IV piggyback (IVPB) over 30 minutes. There is limited data evaluating the safety of IVP administration of 23.4% NaCl.
METHOD(S): We performed a retrospective review of patients who received a dose of 23.4% NaCl (30 mL) at the NYU Langone Health System as either IVP or IVPB. The primary objective was to compare the incidence of adverse events (ADEs) including hypotension, bradycardia, or extravasation.
RESULT(S): Fifty patients were included in this study, with 24 (48%) receiving IVP over 2 (2,5) minutes and 26 (52%) receiving IVPB over 30 (30,30) minutes. The median age was 55 (41,66) years and 60% were female. The most common etiologies of cerebral edema were intracranial hemorrhage (20%), ischemic stroke (16%), and acute liver failure (14%). Indications for 23.4% NaCl included brain herniation (56%), acute increase in ICP (22%), or maintenance of a goal ICP or target sodium (22%). Apart from 2 doses administered peripherally, all doses were given via central access. The time from order entry of 23.4% NaCl to dose completion was significantly faster with IVP administration (IVP 31 [23,69] vs. IVPB 73 [57,126] minutes, p=0.001). No difference was observed in the incidence of ADEs between groups (IVP 7 [29%] vs. IVPB 5 [19%], p=0.411). Hypotension occurred in 6 (25%) vs. 4 (15%) patients (p=0.490) and bradycardia in 2 (8%) vs. 2 (8%) patients (p=1) in the IVP and IVPB arms, respectively. The median percent change from baseline for each hemodynamic variable was less than 3% regardless of administration rate. There were no reported extravasations.
CONCLUSION(S): We did not observe a difference in the incidence of ADEs between IVP and IVPB administration of 23.4% NaCl in patients with heterogeneous etiologies of cerebral edema. In an emergency where time is critical and may impact neurologic function, 23.4% NaCl administered as IVP may be a safe and faster alternative to IVPB administration

Background/UNASSIGNED:Ceftriaxone (CTX) and penicillin G (PCN G) are considered reasonable treatment options for viridans group streptococci (VGS) bloodstream infections, but comparisons between these agents are limited. We evaluated clinical outcomes among patients treated with these agents for complicated VGS bacteremia. Methods/UNASSIGNED:infections, treatment modification or discontinuation due to AEs from therapy, and development of extended-spectrum beta-lactamase resistance. Secondary outcomes included individual safety end points, VGS bacteremia recurrence, hospital readmission, and all-cause mortality. Results/UNASSIGNED: = .139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. No secondary end points differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary composite safety outcome. Conclusions/UNASSIGNED:Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate higher rates of treatment failure, adverse events, or resistance.

Introduction/UNASSIGNED:Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods/UNASSIGNED:A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results/UNASSIGNED:. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.

Background: Viridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia.
Method(s): This was a single-center, retrospective study of adult patients with >=1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality.
Result(s): Of 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56-81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020-0.6771; P= 0.017).
Conclusion(s): Despite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration

BACKGROUND:Oral factor Xa inhibitors (OFXais) may interfere with the heparin antifactor Xa (antiXa) assay. The best method to measure heparin activity during the transition from an OFXai to intravenous (IV) unfractionated heparin (UFH) remains unknown. This study aimed to assess the safety and effectiveness of transitioning from an OFXai to UFH. METHODS:A retrospective analysis was conducted of patients with supratherapeutic antiXa levels on UFH who received either apixaban or rivaroxaban within 72 h prior to UFH initiation at NYU Langone Health (NYULH). The primary objective was to identify the incidence of interference on the heparin antiXa assay due to OFXai exposure in the previous 72 h. The secondary outcomes included the indication for transition to UFH and the rate of thromboembolic and bleeding events. RESULTS:A total of 93 patients with supratherapeutic antiXa activity levels with prior OFXai use were reviewed. Moderate renal impairment, defined as CrCl less than 49 mL/min, was present in 67 (72%) patients. The primary indication for transition from OFXai to UFH was in anticipation for a procedure, and it occurred in 37 (40%) patients. There were three major bleeding events and three clinically relevant non-major bleeding events. No thromboembolic events occurred. CONCLUSIONS:This study assessed the prevalence of supratherapeutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Healthcare systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient's underlying thromboembolic and bleeding risks.

Background. Secondary oral vancomycin prophylaxis (OVP) has been utilized in adults with a history of Clostridioides difficile infection (CDI) while receiving systemic antibiotics to prevent CDI recurrence. However, this practice is poorly described in pediatric patients. Rates of CDI recurrence in pediatric patients range from 10-40% and is associated with morbidity and mortality. This study assessed the efficacy and safety of secondary OVP in pediatric patients with subsequent antibiotic exposure. Methods. This retrospective study evaluated pediatric patients <=18 years with any history of clinical CDI and receiving systemic antibiotics in a subsequent encounter during the time period of 2013-2019. Patients who received OVP 10 mg/kg (up to 125 mg per dose) every 12 hours during concomitant antibiotics were compared to those who did not. The primary outcome was CDI recurrence within 8 weeks following antibiotic exposure. Secondary outcomes included time to recurrence, severity of recurrence, and isolation of vancomycin-resistant enterococci (VRE) from any site. Risk factors for CDI recurrence were assessed using logistic regression. Results. A total of 153 patients were screened for inclusion, of which 32 and 47 patients were assigned to the OVP and no OVP group, respectively. Median age was 8.6 years and the most common comorbidities were malignancy (47%) and immunosuppression (46%). Median time since last CDI to study inclusion was 64.5 days in the OVP group and 90 days in the no OVP group, P=0.320. Compared to the no OVP group, OVP patients had longer hospital stays (5 vs 14 days, P=0.001) and more concomitant antibiotic exposure (8 vs 12.5 days, P=0.001). Median duration of OVP was 12 days. CDI recurrence occurred in 12 patients and was significantly lower in the OVP vs no OVP group (3.1% vs 23.4%; odds ratio, 0.106; 95% confidence interval, 0.013-0.864; P=0.022). VRE was not isolated in any patients. After adjustment in a multivariate analysis, only secondary OVP remained as a protective factor against recurrence (odds ratio, 0.082; 95% confidence interval, 0.009- 0.748; P=0.027). Conclusion. Secondary OVP effectively reduces the risk of recurrent CDI in pediatric patients with a history of CDI while receiving systemic antibiotics. Future prospective studies should validate these findings

Tacrolimus is a mainstay medication for graft-versus-host disease (GVHD) prophylaxis in combination with other immunosuppressive agents. Achieving therapeutic tacrolimus levels is vital in preventing acute GVHD (aGVHD), while supratherapeutic levels may increase risk of toxicity and relapse. We performed a single center retrospective chart review including all adult patients post-allogeneic hematopoietic stem-cell transplantation who received initial tacrolimus continuous intravenous infusion for GVHD prophylaxis between June 1, 2017 and December 31, 2019. The primary outcome was the percent of patients with an initial therapeutic tacrolimus level, defined as 5-12 ng/mL, after empiric weight-based dosing at 0.02 mg/kg/day. Secondary outcomes included evidence of tacrolimus toxicity within seven days of initiation, incidence of aGVHD by day 100, and relapse after six months. An initial therapeutic level was achieved in 47% of patients with a median initial level of 12.4 ng/mL. Fifty-two percent of patients had supratherapeutic levels. No significant nephrotoxicity, hepatotoxicity, or neurotoxicity occurred within a week of starting tacrolimus or at neutrophil engraftment. Grade II-IV aGVHD by day 100 was observed in 22% of patients, and relapse after six months was found in 16% of patients. These results have led to consideration of an empiric 20% dose reduction to 0.016 mg/kg/day or an expanded initial tacrolimus target of 5-15 ng/mL as there was low aGVHD incidence and no increased risk of toxicity.

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.