Management of direct oral anticoagulant drug interactions in hospitalized patients.

Moderate-strong CYP3A4 or Pgp inhibitors and inducers alter direct oral anticoagulant (DOAC) pharmacokinetics. Whether the presence of a DOAC drug-drug interaction (DDI) prompts in- hospital changes in management remains unknown. We identified all hospitalized patients at our institution who were admitted with a clinically relevant DOAC DDI from 01/2021 to 06/2021. Clinically relevant DOAC DDIs were defined as those listed in the prescribing information or FDA CYP3A4/Pgp inhibitors clinical indexes. We assessed the prevalence of DOAC DDIs and categorized their management as: drug stopped, drug held, or drug continued. For drugs that were continued we assessed whether the dose of the DOAC or interacting drug was increased, decreased or unchanged during the admission. We ascertained the number of DOAC DDIs that prompted an automated prescribing alert in our electronic health record (EHR). Finally, we conducted a logistic regression model to compare users of DOACs with DDI who had their regimen adjusted versus those without adjustments, focusing on outcomes of rehospitalization and death, adjusting for age and gender. Among 3,725 hospitalizations with a DOAC admission order, 197 (5%) had a clinically relevant DOAC DDI. The DOAC and the interacting drug were continued at discharge for 124 (63%) hospitalizations. The most frequent adjustments were stopping the interacting drug (73%) and stopping the DOAC (15%). Only 7 (4%) of DOAC DDIs prompted an EHR alert. The adjusted odds ratios for rehospitalizations and death, respectively, among patients whose regimens were adjusted compared to those whose were not, were 1.29 (95% CI, 0.67 to 2.48; P = 0.44) and 1.88 (95% CI, 0.91 to 3.89; P = 0.09). Clinically relevant DDIs with DOACs occur infrequently among hospitalized patients and usually are managed without stopping the DOAC. The clinical impact of such DDIs and subsequent adjustments on thrombotic and hemorrhagic outcomes requires further investigation.

Impact of as needed heparin boluses on supratherapeutic activated partial thromboplastin time in patients managed with extracorporeal membrane oxygenation.

INTRODUCTION: Brigham and Women's Hospital (BWH) historically used titratable weight-based heparin nomograms with as needed boluses managed by extracorporeal membrane oxygenation (ECMO) specialists to achieve a pre-determined goal activated partial thromboplastin time (aPTT). Due to concern amongst providers that as needed boluses may lead to supratherapeutic aPTT's and subsequent bleeding, new nomograms without as needed boluses were implemented. The purpose of this retrospective observational analysis is to provide a comparison in safety and efficacy between the heparin nomograms with as needed boluses and the new nomograms without boluses. METHODS: Adult patients who were cannulated on ECMO and initiated on an approved heparin bolus nomogram (January 1, 2018-December 31, 2019) or an approved heparin no bolus nomogram (October 20, 2020-March 31, 2021) were screened for inclusion. The major endpoint evaluated was the percentage of supratherapeutic aPTTs, defined as an aPTT above the upper limit of the specified nomogram goal, within the first 72 hours. RESULTS: A total of 23 patients were included in the bolus nomogram cohort and 9 patients in the no-bolus nomogram cohort. Within the first 72 hours of initiation, there were 11.5% supratherapeutic aPTTs in the bolus group and 5.1% in the no-bolus group (p=0.101). Overall there was one bleeding event in the no-bolus group (11.1%) and seven in the bolus group (30.4%) (p=0.26). There were no thromboembolic events in either group. CONCLUSION: Overall, there was no difference found in percentage of supratherapeutic aPTTs within the first 72 hours of heparin initation between the bolus and no-bolus nomograms.

Anticoagulation-Associated Adverse Drug Events in Hospitalized Patients Across Two Time Periods.

PURPOSE: Anticoagulants often cause adverse drug events (ADEs), comprised of medication errors and adverse drug reactions, in patients. Our study objective was to determine the clinical characteristics, types, severity, cause, and outcomes of anticoagulation-associated ADEs from 2015-2020 (a contemporary period following implementation of an electronic health record, infusion device technology, and anticoagulant dosing nomograms) and to compare them with those of a historical period (2004-2009). METHODS: We reviewed all anticoagulant-associated ADEs reported as part of our hospital-wide safety system. Reviewers classified type, severity, root cause, and outcomes for each ADE according to standard definitions. Reviewers also assessed events for patient harm. Patients were followed up to 30 days after the event. RESULTS: Despite implementation of enhanced patient safety technology and procedure, ADEs increased in the contemporary period. In the contemporary period, we found 925 patients who had 984 anticoagulation-associated ADEs, including 811 isolated medication errors (82.4%); 13 isolated adverse drug reactions (1.4%); and 160 combined medication errors, adverse drug reactions, or both (16.2%). Unfractionated heparin was the most frequent ADE-related anticoagulant (77.7%, contemporary period vs 58.3%, historical period). The most frequent anticoagulation-associated medication error in the contemporary period was wrong rate or frequency of administration (26.1%, n = 253), with the most frequent root cause being prescribing errors (21.3%, n = 207). The type, root cause, and harm from ADEs were similar between periods. CONCLUSIONS: We found that anticoagulation-associated ADEs occurred despite advances in patient safety technologies and practices. Events were common, suggesting marginal improvements in anticoagulant safety over time and ample opportunities for improvement.

Implementation of Pharmacy Executive Quality and Safety Walkrounds at a Tertiary Academic Medical Center.

Background: Executive Quality and Safety WalkRounds (EWRs) is a tool that engages department leadership in discussion with the front-line employees to solicit feedback to improve quality and safety. The purpose of this study was to evaluate the impact of the implementation of pharmacy department specific EWRs on quality and safety at a tertiary academic medical center. Method: This was a single-center, retrospective analysis conducted at Brigham and Women's Hospital between November 2016 and November 2019. This study aimed to analyze the implementation of EWRs conducted every other month throughout various service areas and satellites of the pharmacy department. Data evaluated included the number of EWRs conducted, the specific areas visited, the total number of action items recommended by the staff, along with the total number of action items that were completed or remained in process. Results: During the study period, 17 visits were completed in 12 different BWH pharmacy sub-departments. A total of 98 operational, technological, and environmental action items were recommended by staff to improve quality and safety. Of the 98 action items documented, 95 (96.9%) were completed by time of our analysis. Conclusion: Pharmacy department EWRs are an important and systematic process of communication between the pharmacy leadership and frontline staff. Pharmacy department EWRs have resulted in safety and quality improvements at different levels in the pharmacy department. The EWRs program at the pharmacy department was effective in identifying and completing safety initiatives to improve the safety culture of the department.

Intravenous levothyroxine stewardship program at a tertiary academic medical center.

PURPOSE: Based on the pharmacokinetic profile of levothyroxine, a 3-day hold guideline for adult patients ordered for intravenous (IV) levothyroxine was implemented at a tertiary academic medical center. The purpose of this study was to evaluate the impact of the implementation of an IV levothyroxine hold guideline. METHODS: This single-center, retrospective analysis identified patients ordered for IV levothyroxine during a 13-week period before and after implementation of the guideline. The primary outcome was guideline adherence, defined as full implementation of the 3-day hold. Secondary outcomes included the number of IV levothyroxine administrations avoided in the post-guideline group, extrapolated yearly cost avoidance (EYCA) after guideline implementation, reasons for guideline non-adherence, and number of safety reports involving IV levothyroxine. RESULTS: A total of 166 and 134 patients met inclusion criteria for the pre- and post-guideline groups, respectively. Guideline adherence was observed in 94 (70.1%) patients, resulting in 276 vials saved in the 13-week post-guideline period, which translated to an EYCA of $139,877. Forty orders (29.9%) were non-adherent to the guideline, with the most common reason stated as nil per os (NPO). No difference in safety outcomes was seen between the pre- and post-guideline groups, as evidenced by 1 safety report in each group. CONCLUSION: We observed a high rate of adherence to an IV levothyroxine hold guideline. This was associated with a substantial cost savings over the study period with no increase in reported safety events. To our knowledge, this is the first published report of an inpatient IV levothyroxine 3-day hold guideline.

Evaluation of Cost, Workflow, and Safety of Implementing a Vial Transfer Device for Ready-to-Mix Drugs at an Academic Medical Center.

OBJECTIVE: To evaluate the cost, workflow, and safety of implementing a vial transfer device system. METHODS: In this retrospective analysis, pharmacy systems and electronic health record reports identified high-volume and high-cost medications prepared by a Vial2Bag® (V2B) system from July 2017 to June 2018. The major outcome was the extrapolated yearly cost avoidance (EYCA) from utilization of a V2B system, calculated by subtracting total costs of the V2B system from total cost of ready-to-use products and locally compounded sterile products. Secondary outcomes included a workflow and safety analysis. RESULTS: Implementing a V2B system led to a total EYCA of $2 295 261. A total of 283 209 potential V2B units were available for dispensing from automated dispensing systems and 41 082 yearly sterile product room units were avoided. A 0.02% safety report incidence per V2B administration was calculated at our institution. CONCLUSION: Use of a V2B system resulted in a substantial cost avoidance compared to purchasing commercial products and preparing locally compounded sterile products. The V2B system appears to be a safe addition to further optimize workflow but may require further investigation in prospective analyses.

Potassium Chloride Sustained Release Dosing Pathway in an Academic Medical Center.

Potassium supplementation can be administered intravenously or orally with either immediate release or sustained release formulations. Sustained release potassium chloride allows for delayed absorption and peak effects. In the inpatient setting, it is important to monitor and prevent both hypokalemia and hyperkalemia. Our tertiary-care academic hospital created a clinical pathway for sustained release potassium chloride supplementation in the inpatient population. Our clinical pathway for sustained release potassium chloride creates dosing restrictions designed to prevent hyperkalemia, while allowing exceptions for patients with high requirements.

Fibrinolytic and Anticoagulation Therapy in Patients Undergoing Ultrasound-Assisted Catheter-Directed Thrombolysis for Pulmonary Embolism.

BACKGROUND: Ultrasound-assisted, catheter-directed thrombolysis (UA-CDT) relieves right ventricular stress without a significant increase in the risk of bleeding compared to systemic thrombolysis. Although concomitant anticoagulation is provided to prevent thrombus expansion, the optimal anticoagulation regimen in patients receiving UA-CDT remains unknown. OBJECTIVE: We sought to describe anticoagulation practices for patients receiving UA-CDT. METHODS: Patients receiving UA-CDT for acute pulmonary embolism (PE) between Jan 1, 2013 to Sept 30, 2014 at a single center were analyzed. We collected patient characteristics, fibrinolytic and anticoagulant usage as well as clinical outcomes. RESULTS: Fourteen patients were included in the final analysis. The mean alteplase dose was 16.8 ± 5.6 mg and 24.3 ± 3.4 mg in unilateral and bilateral PE, respectively. Mean unfractionated heparin (UFH) rates were 7.4 (±2.17) IU/kg/hr and 12.4 (±3.1) IU/kg/hr during and after fibrinolytic therapy, respectively. The median aPTT was 42.4 sec [IQR 34.5-51.8] and 77.9 sec [IQR 66.5-96.8] during and after fibrinolytic therapy, respectively. There were no recurrent VTE within 30 days of hospital discharge. One patient had a major bleeding event (intracranial hemorrhage). CONCLUSION: In patients with acute PE, our institution utilized low levels of anticoagulation during fibrinolytic administration and therapeutic doses after completion of fibrinolytic infusion. Standardized protocols for anticoagulation during UA-CDT are warranted.

Evaluation of a clinical pathway for sedation and analgesia of mechanically ventilated patients in a cardiac intensive care unit (CICU): The Brigham and Women's Hospital Levine CICU sedation pathways.

BACKGROUND: Intravenous sedation and analgesia are important therapies during mechanical ventilation (MV). However, daily interruption of these medications is associated with improved outcomes in mechanically ventilated patients. We tested a clinical pathway for the use of sedation and analgesia during MV in a cardiac intensive care unit (CICU). METHODS AND RESULTS: We evaluated all mechanically ventilated patients in a CICU during two phases: phase 1 prior to pathway implementation (PRE) and phase 2 post-pathway implementation (POST). A total of 198 patients (98 PRE and 100 POST) and 1012 days of intubation (574 PRE and 434 POST) were included in this analysis. We found an increase in the frequency of daily interruptions of sedation post-implementation (49.3% PRE and 58.4% POST, p=0.0041). There was a significant decrease in the mean duration of MV in the POST vs PRE periods (5.0±2.3 vs 6.1±2.8 days, p=0.015). There was also a significant decrease in total neuroimaging studies (9 vs 49, p=0.001) and a trend toward a decrease in tracheostomies (3.0% vs 6.1%, p=0.33). Mean CICU length of stay (LOS) and hospital LOS respectively were 10.4 days and 16.8 days PRE and 10.4 days and 17.9 days POST (p=0.99 and p=0.55). Mortality did not differ (PRE 36.7% vs POST 32.0% p=0.55). CONCLUSIONS: Implementation of a pragmatic pathway for sedation and analgesia in a CICU was associated with an increase in the daily interruption of sedation and a corresponding decrease in the duration of MV days and the need for neuroimaging.