Improving Medication Safety in an ICU.

ABSTRACT: Reported medication errors in an ICU at an academic teaching hospital raised concerns about adherence to safety protocols, including barcode scanning before medication administration. A group of nurse leaders, bedside nurses, and pharmacists formed a medication safety task force to increase compliance with barcode scanning and reduce reported medication errors in which failure to scan was a contributing factor.Three task force members observed nurses' workflow in ICU medication administration. The members observed three nurses administer medications before scanning the barcode and three other nurses scan medications in a location where they were unable to see alerts on the computer. After the observations, the task force implemented three interventions: medication tables to provide a surface in front of the computer where medications could be placed when scanning; standardized workflow; and nursing staff education. Task force members then conducted postimplementation observations to evaluate improvement in barcode scanning compliance.In the postintervention observations, all medications were scanned in front of the computer before administration, an increase of 27.3 percentage points (from 72.7% preintervention) in the barcode scanning compliance rate. The ICU also went 17 months in the postintervention period without a reported medication administration error in which failure to scan was a contributing factor.The task force's observation of medication administration led to interventions that made it easier for nurses to adhere to best practice. Medication tables were a simple, sustainable intervention that used human factors principles to increase barcode scanning compliance.

Characteristics of delirium and its association with sedation and in-hospital mortality in patients with COVID-19 on veno-venous extracorporeal membrane oxygenation.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods: We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU (CAM-ICU) when patients scored-3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO. Results: Of 47 patients (median age = 51), 6 were in a persistent coma and 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n = 21) and non-survivors (n = 26) was first detected at a similar time point (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p = 0.06) and significantly prolonged delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0(6,23), p = 0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p = 0.04). The proportion of delirium-present days correlated with RASS (r = 0.64, p < 0.001), the proportions of days on VV-ECMO with a neuromuscular blocker (r = -0.59, p = 0.001), and with delirium-unassessable exams (r = -0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality. Conclusion: Longer duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Personalised recommendations for hospitalised patients with Acute Kidney Injury using a Kidney Action Team (KAT-AKI): protocol and early data of a randomised controlled trial.

INTRODUCTION: Although studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients. METHODS AND ANALYSIS: KAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid-base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8-51.5) min. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion. TRIAL REGISTRATION NUMBER: NCT04040296.

The Impact of an Antithrombotic Stewardship Program on Heparin-Induced Thrombocytopenia Management.

Background: An antithrombotic stewardship program was implemented to reduce IV DTI use and increase fondaparinux and direct oral anticoagulant (DOAC) use for suspected or confirmed Heparin-induced thrombocytopenia (HIT). Objectives: This study evaluated the impact of an antithrombotic stewardship program on IV DTI utilization in patients with HIT. Methods: A retrospective analysis of adults receiving IV DTIs or fondaparinux from July 2016 to July 2017 (pre-stewardship) and October 2017 to July 2019 (post-stewardship) was conducted. Results: The median duration of IV DTI administration was not significantly different in HIT-negative patients between the pre- and post-stewardship cohorts (1.6 days (25th percentile (p25), 75th percentile (p75): .5, 3.3) vs 1.7 days (p25, p75: .9, 3.9), P = .31). The median duration of IV DTI administration in HIT-positive patients was 9.9 days (p25, p75: 7.6, 21.0) pre-stewardship and 7.3 days (p25, p75: 4.8, 16.5) post-stewardship (P = .18). For HIT-positive patients, the time from HIT diagnosis to discharge was 12.8 days (p25, p75: 8.9, 24.9) and 9.2 days (p25, p75: 4.0, 18.1) in the pre- and post-stewardship cohorts, respectively (P = .07). Fondaparinux and DOAC prescribing rates were 40.7% and 62.2% in the pre- and post-stewardship cohorts, respectively (P = .09). The percentage of patients with no contraindications to IV DTI alternatives receiving these agents increased from 31.2% to 78.6% (P = .01) following stewardship implementation. Conclusions: Intravenous DTI alternative utilization increased significantly after stewardship implementation. Stewardship implementation was associated with a non-statistically significant trend towards decreased IV DTI utilization and decreased length of stay for HIT-positive patients.

Analgosedation in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation Support.

Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized intervention for cardiopulmonary failure. Analgosedation during ECMO support is essential to ensure adequate pain and agitation control and ventilator synchrony, optimize ECMO support, facilitate patient assessment, and minimize adverse events. Although the principles of analgosedation are likely similar for all critically ill patients, ECMO circuitry alters medication pharmacodynamics and pharmacokinetics. The lack of clinical guidelines for analgosedation during ECMO, especially at times of medication shortage, can affect patient management. Here, we review pharmacological considerations, protocols, and special considerations for analgosedation in critically ill adults receiving ECMO support.

Comparison of Clinical Scoring Tools to Predict Heparin-Induced Thrombocytopenia in Cardiac Surgery.

The 4Ts and HIT-Expert Probability (HEP) scoring tools for heparin-induced thrombocytopenia (HIT) have not been validated in cardiac surgery patients, and the reported sensitivity and specificity of the Post-Cardiopulmonary Bypass (CPB) scoring tool vary widely in the 2 available analyses. It remains unclear which of the available scoring tools most accurately predicts HIT in this population. Forty-nine HIT-positive patients who underwent on-pump cardiac surgery within a 6-year period were loosely matched to 98 HIT-negative patients in a 1:2 case-control design. The 4Ts, HEP, and CPB scores were calculated for each patient. Sensitivity and specificity of each tool were calculated using standard cut-offs. The Youden method was utilized to determine optimal cut-offs within receiver operating characteristic (ROC) curves of each score, after which sensitivities and specificities were recalculated. Using standard cut-offs, the sensitivities for the CPB, HEP, and 4Ts scores were 100%, 93.9%, and 69.4%, respectively. Specificities were 51%, 49%, and 71.4%, respectively. The AUC of the scoring tool ROC curves were 0.961 for the CPB score, 0.773 for the HEP score, and 0.805 for the 4Ts score. Using the Youden method-derived optimal cut-off of  ≥3 points on the CPB score, sensitivity remained 100% with improved specificity to 88.9%. The CPB score is the preferred HIT clinical scoring tool in adult cardiac surgery patients, whereas the 4Ts score performed less effectively. A cut-off of ≥ 3 points on the CPB score could increase specificity while preserving high sensitivity, which should be validated in a prospective evaluation.

Quality of Heart Failure Care in the Intensive Care Unit.

Patients with heart failure (HF) who are seen in an intensive care unit (ICU) manifest the highest-risk, most complex and most resource-intensive disease states. These patients account for a large relative proportion of days spent in an ICU. The paradigms by which critical care is provided to patients with HF are being reconsidered, including consideration of various multidisciplinary ICU staffing models and the development of acute-response teams. Traditional HF quality initiatives have centered on the peri- and postdischarge period in attempts to improve adherence to guideline-directed therapies and reduce readmissions. There is a compelling rationale for expanding high-quality efforts in treating patients with HF who are receiving critical care so we can improve outcomes, reduce preventable harm, improve teamwork and resource use, and achieve high health-system performance. Our goal is to answer the following question: For a patient with HF in the ICU, what is required for the provision of high-quality care? Herein, we first review the epidemiology of HF syndromes in the ICU and identify relevant critical care and quality stakeholders in HF. We next discuss the tenets of high-quality care for patients with HF in the ICU that will optimize critical care outcomes, such as ICU staffing models and evidence-based management of cardiac and noncardiac disease. We discuss strategies to mitigate preventable harm, improve ICU culture and conduct outcomes review, and we conclude with our summative vision of high-quality of ICU care for patients with HF; our vision includes clinical excellence, teamwork and ICU culture.

Continuous-infusion von Willebrand factor concentrate is effective for the management of acquired von Willebrand disease.

Acquired von Willebrand disease (aVWD) is a rare disorder associated with a reduction in von Willebrand factor (VWF) activity, leading to increased bleeding risk. Monoclonal gammopathy of undetermined significance (MGUS) is the most common cause of lymphoproliferative disorder-associated aVWD and is caused by accelerated clearance of circulating VWF. Standard VWF replacement protocols for congenital VWD based on intermittent bolus dosing are typically less effective for aVWD because of antibody-mediated clearance. Intermittent bolus dosing of VWF concentrates often leads to inadequate peak response and profoundly shortened VWF half-life in aVWD. Intravenous immune globulin (IVIG) has demonstrated efficacy in aVWD; however, treatment effect is delayed up to 4 days, limiting its efficacy in acutely bleeding patients. We report the successful use of continuous-infusion VWF concentrate (with or without concomitant IVIG) in 3 patients with MGUS-associated aVWD who had demonstrated an inadequate response to bolus dosing. VWF concentrate doses required in this cohort were higher than typical doses for bleeding treatment in congenital VWD. This report illustrates that continuous-infusion VWF concentrate administration with or without intravenous immunoglobulin rapidly achieves target ristocetin cofactor activity and provides adequate hemostasis in aVWD associated with immunoglobulin G MGUS.

Guideline recommendations, clinical trial data, and new and emerging therapies.

Nearly 93 million American adults have hyperlipidemia, a major risk factor for the development of atherosclerotic cardiovascular disease. Use of HMG-CoA reductase inhibitors (ie, statins) and ezetimibe have decreased hypercholesterolemia's prevalence in the past decade, but poor adherence is common and leads to scenarios where patients do not derive the greatest possible benefit. In addition, statin resistance may play a role when patients' LDL-C levels are not lowered to the expected extent despite good medication adherence. When statins fail to control hyperlipidemia, guidelines recommend furthering treatment by adding ezetimibe or a PCSK9 inhibitor. In November 2018, the American College of Cardiology and the American Heart Association updated their hyperlipidemia guideline. This revision recommends a more aggressive approach to hyperlipidemia. In patients who fail to respond to or cannot tolerate statins or ezetimibe, PCSK9 inhibitors are a reasonable treatment option. Large outcomes trials have compared the currently approved PCSK9 inhibitors with placebo and established that PCSK9 inhibitors lowered LDL-C by more than 50% below the statin-treated baseline and reduce cardiovascular outcomes. In addition, bempedoic acid, lomitapide, and evinacumab are available options that may be instituted in select patients. In development is inclisiran, a small interfering RNA molecule, which antagonizes PCSK9 production. With good adherence and the use of a greater assortment of medications, patients may experience atherogenic lipoprotein lowering, leading to a decrease in cardiovascular disease.

COVID-19 pandemic: Challenges and solutions from the cardiology pharmacist's perspective.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re-evaluated daily processes and therapies used to treat COVID-19 patients within our institutions from a cardiovascular perspective and share what we have learned. To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID-19 patients by drawing on the experiences of cardiology pharmacists across the country. On March 26, 2020, a conference call was convened composed of 24 cardiology residency-trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID-19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. The collaborative of pharmacists found for the ST-elevation myocardial infarction patient, many institutions were diverting COVID-19 rule-out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision-making processes with their preceptors and assist as pharmacist extenders. Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID-19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times.

Optimization of Lipid-Lowering Therapy for High Cardiovascular Risk Patients Through Electronic Medical Record Reporting and Pharmacist Evaluation.

BACKGROUND: Identification of high cardiovascular risk patients on suboptimal lipid-lowering therapy (LLT) may be possible through electronic medical record (EMR) reporting, presenting an opportunity for pharmacist involvement in optimizing drug regimens. OBJECTIVES: To (a) identify high cardiovascular risk patients with opportunities for LLT optimization through EMR reporting and (b) evaluate effectiveness of pharmacist review and treatment algorithm on recommending treatment modifications compared with algorithm application alone. METHODS: We generated an EMR report to identify adult patients aged 21-75 years with clinical atherosclerotic cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) level ≥ 70 mg/dL during a 6-month period and collected pertinent data elements. We selected a subgroup of patients for remote pharmacist review and determined recommendations based on our predefined LLT optimization algorithm and pharmacist clinical judgment. One pharmacist was responsible for making all recommendations and communicated potential treatment modification to primary care providers via email and/or EMR messaging. We tracked provider acceptable/rejection rate to all recommendations made. We also compared recommendations based on using the algorithm alone to combining pharmacist chart review and algorithm and examined reasons for any discrepancies. RESULTS: 941 patients met inclusion criteria, with 399 patients (42.4%) not currently on any LLT. At baseline, 249 patients (25.3%) were on a high-intensity statin, and 19 (1.9%) were on a proprotein convertase subtilisin/kexin type 9 inhibitor. A subgroup of 34 patients were reviewed, of which 30 (88.2%) were on suboptimal therapy despite not achieving LDL-C goals. The pharmacist recommended to intensify statin therapy for 16 patients (47.1%), initiate nonstatin therapy for 9 patients (26.5%), and initiate statin therapy in 5 patients (14.7%). Pharmacist recommendation acceptance rate was 53.3%, with no response received in 26.6% of cases. The algorithm evaluation alone yielded the same recommendation as the combined pharmacist review with algorithm in 30 (88.2%) of the cases and differed in 4 cases. CONCLUSIONS: The underutilization of LLT among high cardiovascular risk patients remains a growing issue despite effective treatment options with cardiovascular benefits. Pharmacists may be able to identify these patients by using reportable EMR data elements and applying a treatment optimization algorithm to make therapy recommendations and improve outcomes. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no relevant declarations of interest to disclose. This study was presented as a poster presentation at the APhA Annual Meeting, March 2019, Seattle, WA, and as a platform presentation at the Eastern States Conference, May 2019, Hershey, PA.

The Development and Impact of Hemostatic Stewardship Programs.

The approval of several new clotting factor concentrates and anticoagulation antidotes has resulted in increased complexity and cost of care. A multidisciplinary hemostatic stewardship program is essential to optimize utilization of these resources. This article summarizes the authors' approach to the stewardship of clotting factor concentrates and anticoagulation antidotes.

Successful use of emicizumab in a patient with refractory acquired hemophilia A and acute coronary syndrome requiring percutaneous coronary intervention.

ABSTRACT: We report a patient with a high-titer factor VIII inhibitor refractory to immunosuppression. He initially presented with myocardial infarction requiring percutaneous coronary intervention (PCI) with bare metal stent placement. Despite Feiba prophylaxis, inadequate hemostasis prompted premature discontinuation of dual antiplatelet therapy (DAPT). Fifteen weeks later, the patient presented with a left anterior descending artery in-stent restenosis. This case report examines the Key Clinical Question of how to manage in-stent restenosis in a patient with acquired hemophilia A (AHA). After multidisciplinary discussions including hematology, cardiology, cardiac surgery, laboratory medicine, and pharmacy, emicizumab was initiated to facilitate PCI. Four weeks after emicizumab initiation, the patient underwent successful PCI with drug-eluting stent placement. Five months after discharge, he remains without signs or symptoms of cardiac disease or bleeding on DAPT and emicizumab. This case provides evidence of the potential of emicizumab for bleeding prophylaxis in AHA.

Identification of Cost-Saving Opportunities for the Use of Antithrombin III in Adult and Pediatric Patients.

Thrombate III is a human plasma-derived antithrombin III (AT-III) often utilized in patients on extracorporeal membrane oxygenation (ECMO) with suspected AT-III-mediated heparin resistance. It is supplied as 500-U and 1000-U vials, costing US$4.66 per unit. Literature is limited in describing the clinical value of AT-III in relation to its high cost. The primary objective was to determine conditions of use and associated cost of potentially unnecessary utilization of AT-III at The Johns Hopkins Hospital. Secondary objectives included evaluating the effect of AT-III on anticoagulation parameters and the overall cost utilized and wasted on AT-III. A retrospective cohort study was performed. The primary end point was the total cost associated with potentially unnecessary utilization of AT-III. There were 326 doses of AT-III administered to 65 patients in 2014. There were 177 (54%) potentially unnecessary doses associated with a cost of US$541 634. Antithrombin III repletion significantly increased median AT-III levels in non-ECMO and ECMO patients compared to baseline (non-ECMO: 62% vs 81%, P < .01; ECMO: 63% vs 81%, P < .01); however, 37.3% of ECMO and 49% of non-ECMO patients had therapeutic anticoagulation monitoring parameters prior to administration. A total cost of US$688 478 was spent on administered AT-III and US$417 194 (38%) was wasted. Utilizing restriction criteria and a new dosing strategy potentially results in estimated annual savings of US$556 000. Utilizing restriction criteria and alternative dosing strategies to mitigate waste and unnecessary use has the potential to result in significant cost savings.

Safety of novel oral anticoagulants compared with uninterrupted warfarin for catheter ablation of atrial fibrillation.

BACKGROUND: The novel oral anticoagulants (NOACs) are used for stroke prevention in atrial fibrillation (AF), but their safety and efficacy in the periablation period are not well established. Additionally, no standard procedure for managing periprocedural and intraprocedural anticoagulation has been established. OBJECTIVE: To evaluate the frequency of hemorrhagic and thrombotic events as well as periprocedural management strategies of NOACs compared with warfarin as anticoagulation therapy for AF ablation. METHODS: This was a retrospective cohort study from a prospective AF ablation registry maintained at a large, academic medical center. RESULTS: A total of 374 cases (173 warfarin, 123 dabigatran, 61 rivaroxaban, and 17 apixaban) were included in the analysis. The overall hemorrhagic/thrombotic event rate was 14.2 % (major hemorrhage 2.7%, minor hemorrhage 11.2%, thrombotic stroke 0.5%). The frequency of minor hemorrhage was significantly higher with warfarin compared with dabigatran (15% vs 5.7%, P = 0.012). The average heparin dose required to reach the goal activated clotting time (ACT) was 5600 units for warfarin, 12 900 units for dabigatran (P < 0.001), 15 100 units for rivaroxaban (P < 0.001), and 14 700 units for apixaban (P < 0.001). The average time in minutes to reach the goal ACT was significantly longer, compared with warfarin, for dabigatran (57 vs 28, P < 0.001), rivaroxaban (63 vs 28, P < 0.001), and apixaban (72 vs 28, P < 0.001). CONCLUSIONS: Compared with warfarin, periprocedural anticoagulation with dabigatran resulted in fewer minor hemorrhages and total adverse events after AF ablation. Patients anticoagulated with NOACs required larger doses of heparin and took longer to reach the goal ACT compared with patients anticoagulated with warfarin.

Incidence of amiodarone hypersensitivity in patients with previous allergy to iodine or iodinated contrast agents.

STUDY OBJECTIVE: To determine the incidence and nature of allergic reactions to amiodarone in hospitalized patients with a listed allergy to iodine or iodinated radiocontrast agents. DESIGN: Retrospective medical record review. SETTING: Two academic medical centers. PATIENTS: A total of 234 sequential hospitalized patients with a listed iodine and/or iodinated radiocontrast agent allergy who received oral or intravenous amiodarone between January 2006 and December 2010. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data, as well as documentation of an allergic reaction to amiodarone, were collected for each patient from electronic medical records. Mean ± SD age was 69 ± 12 years, and 51% were male. Of the 234 patients, 167 (71%) had a listed previous allergy to iodinated contrast agents, 55 (24%) to iodine, and 12 (5%) to both. Patients received an average inpatient total dose of 2.9 ± 3.2 g of either oral (106 patients [45%]), intravenous (39 patients [17%]), or both oral and intravenous (89 patients [38%]) amiodarone. Only 1 (0.4%) of the 234 patients was identified as having a probable allergic reaction to amiodarone (score of 6 on the Naranjo adverse drug reaction probability scale). One additional patient receiving intravenous amiodarone experienced a rash that was determined to be caused by an antibiotic. All other patients received amiodarone without any identifiable allergic reactions. CONCLUSION: The incidence of hypersensitivity reaction to amiodarone in hospitalized patients with a listed allergy to iodine or iodinated contrast agents was less than 1%, and all identified reactions were without long-term sequelae. Allergy to iodine and iodinated contrast agents may not be a valid absolute contraindication to amiodarone administration in the inpatient setting.