Droxidopa for Vasopressor Weaning in Critically Ill Patients with Persistent Hypotension: A Multicenter, Retrospective, Single-Arm Observational Study.

BACKGROUND: Persistent vasopressor requirements are a common reason for delayed liberation from the intensive care unit (ICU) and adjunct oral agents are sometimes used to hasten time to vasopressor discontinuation. We sought to describe the use of droxidopa for vasopressor weaning in critically ill patients with prolonged hypotension. MATERIALS AND METHODS: This retrospective, single-arm, observational study included adult patients admitted to an ICU at two academic centers between 06/2016-07/2023 who received droxidopa for vasopressor weaning. Patients who received droxidopa prior to admission or for another indication were excluded. The primary outcome was time to vasopressor discontinuation, defined as when vasopressors were stopped and remained off for at least 24 h. Secondary outcomes included rates of tachycardia and hypotension post-initiation, norepinephrine equivalents pre- and post-initiation, concomitant oral agent use, and dosing. A subgroup analysis was conducted in patients receiving droxidopa via feeding tubes. RESULTS: A total of 30 patients met inclusion criteria. Median age was 62 years old, 12 (40%) were female, and 73% were in a cardiac/cardiac surgical ICU. Patients were on vasopressors for a median of 16 days prior to droxidopa initiation. Median (IQR) time to vasopressor discontinuation was 70 h (23-192) and norepinephrine equivalents decreased immediately after initiation (0.08 vs 0.02 mcg/kg/min, p < 0.001). MAP increased after droxidopa initiation (68.8 vs 66.5 mm Hg, p = 0.008) while heart rates were unchanged (86 vs 84 BPM, p = 0.37) after initiation. Patients who weaned from vasopressors within 72 h versus longer than 72 h after droxidopa initiation were more likely to be on lower norepinephrine equivalents prior to initiation (0.05 vs 0.12 mcg/kg/min, p = 0.013). Feeding tube administration did not impact time to vasopressor discontinuation (p = 0.93). CONCLUSIONS: Droxidopa may be considered an adjunct therapy for vasopressor weaning. Effects were similar when analyzing patients receiving droxidopa via feeding tube.

Development and Implementation of a Multicomponent Protocol to Promote Sleep and Reduce Delirium in a Medical Intensive Care Unit.

BACKGROUND: Evidence suggests that poor sleep increases risk of delirium. Because delirium is associated with poor outcomes, institutions have developed protocols to improve sleep in critically ill patients. OBJECTIVE: To assess the impact of implementing a multicomponent sleep protocol. METHODS: In this prospective, preimplementation and postimplementation evaluation, adult patients admitted to the medical intensive care unit (ICU) over 42 days were included. Outcomes evaluated included median delirium-free days, median Richards-Campbell Sleep Questionnaire (RCSQ) score, median optimal sleep nights, duration of mechanical ventilation (MV), ICU and hospital length of stay (LOS), and in-hospital mortality. RESULTS: The preimplementation group included 78 patients and postimplementation group, 84 patients. There was no difference in median delirium-free days (1 day [interquartile range, IQR, = 0-2.5] vs 1 day [IQR = 0-2]; P = 0.48), median RCSQ score (59.4 [IQR = 43.2-71.6] vs 61.2 [IQR = 49.9-75.5]; P = 0.20), median optimal sleep nights (1 night [IQR = 0-2] vs 1 night [IQR = 0-2]; P = 0.95), and in-hospital mortality (16.7% vs 17.9%, P = 1.00). Duration of MV (8 days [IQR = 4-10] vs 4 days [IQR = 2-7]; P = 0.03) and hospital LOS (13 days [IQR = 7-22.3] vs 8 days [IQR = 6-17]; P = 0.05) were shorter in the postimplementation group, but both were similar between groups after adjusting for age and severity of illness. CONCLUSIONS AND RELEVANCE: This report demonstrates that implementation of a multicomponent sleep protocol in everyday ICU care is feasible, but limitations exist when evaluating impact on measurable outcomes. Additional evaluations are needed to identify the most meaningful interventions and best practices for quantifying impact on patient outcomes.

Initiative to deprescribe high-risk drugs for older adults presenting to the emergency department after falls.

BACKGROUND: Over 35 million falls occur in older adults annually and are associated with increased emergency department (ED) revisits and 1-year mortality. Despite associations between medications and falls, the prevalence of fall risk-increasing drugs remains high. Our objective was to implement an ED-based medication reconciliation for patients presenting after falls and determine whether an intervention targeting high-risk medications was related to decreased future falls. METHODS: This was an observational prospective cohort study at a single site in the United States. Adults 65 years and older presenting to the ED after falls had a pharmacist review their medicines. Pharmacists made recommendations to taper, stop, or discuss medications with the primary clinician. At 3, 6, and 12 months, we recorded the number of fall-related return ED visits and determined if recommended medication changes had been implemented. We compared the rate of return visits of patients who had followed the medication change recommendations and those who received recommendations but had no change in their medications using chi-square tests. RESULTS: A total of 577 patients (mean age 81 years, 63.6% female) were enrolled of 1509 potentially eligible patients. High-risk medications were identified in 310 patients (53.7%) who received medication recommendations. High-risk medications were associated with repeat fall-related visits at 12 months (risk difference 8.1% [95% confidence interval 0.97-15.0]). A total of 134 (43%) patients on high-risk medications had evidence of medication modification. At 12 months, there was no statistically significant difference in return fall visits between patients who had modifications to medications compared with those who had not implemented changes (p = 0.551). CONCLUSIONS: Our findings identified opportunities for medication optimization in over half of emergency visits for falls and demonstrated that medication counseling in the ED is feasible. However, evaluation of the effect on future falls was limited.

Evaluation of a Multimodal Heparin Laboratory Monitoring Protocol in Adult Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. OBJECTIVE: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. METHODS: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. RESULTS: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). CONCLUSION: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration.

Reduced Time to Procedure for Gastrointestinal Bleeding After Warfarin Reversal With Four-Factor Complex Concentrate as Compared to Plasma.

Background: Bleeding is a serious adverse effect of vitamin K antagonists (VKAs). Anticoagulation reversal is required in some acute cases. This is usually accomplished by plasma transfusion or four-factor prothrombin complex concentrate (4F-PCC). The aim of this study was to gain insight into the clinical course of patients with gastrointestinal (GI) bleeding who require VKA reversal. Methods: Medical records were collected from two centers from patients who presented to the emergency department (ED) for GI bleeding and received 4F-PCC or plasma for VKA reversal between January 2015 and December 2020. ED, hospital, intensive care unit (ICU) length of stay (LOS) as well as time from admission to GI procedure were determined. Results: 4F-PCC patients (n = 49) as compared to plasma (n = 63) patients were found to have a greater number of comorbidities (average of 4.2 vs. 2.7 comorbidities/patient) and more ICU admissions (47% vs. 21%). Time to GI procedure was significantly decreased in the 4F-PCC group (median (interquartile range (IQR)) 19.47 (9.23 - 30.25) vs. 27.88 (21.38 - 45.00) h; P = 0.01). When adjusting for comorbidities, differences in time to GI procedures were also significant in favor of 4F-PCC regardless of any comorbidities (P = 0.014), in atrial fibrillation (P = 0.045) and in hypertension (P = 0.02). The 4F-PCC patients had shorter LOS in the ED and ICU. Conclusions: Our study demonstrated that compared to plasma, 4F-PCC was utilized in more acutely ill patients with higher rates of comorbidities and ICU admission. Nevertheless, the patients who received 4F-PCC had faster access to GI procedure and shorter ED and ICU LOS.

Accuracy of a modified 4Ts score in predicting heparin-induced thrombocytopenia in critically ill patients: A pilot study.

PURPOSE: Thrombocytopenia is common among critically ill patients and heparin-induced thrombocytopenia (HIT) is often on the differential. Professional guidelines recommend calculating a pre-test probability score before performing HIT testing. The 4Ts score is widely utilized but accuracy has been questioned in critically ill patients. The HIT Expert Probability (HEP) score is available, but complexity limits use. Our objective was to compare a modified intensive care unit (ICU)-4Ts score to available scoring tools. MATERIALS AND METHODS: This was a single-center retrospective pilot study. Adult ICU patients that were tested for HIT and had a documented 4Ts score were included. A blinded investigator retrospectively calculated the HEP and ICU-4Ts score. Receiver operating characteristics (ROC) area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were compared. RESULTS: In 194 included patients, ROC AUC was significantly higher for the ICU-4Ts compared to the 4Ts score (0.80 versus 0.66, respectively; p = 0.044). The ICU-4Ts score had the highest specificity, PPV, and NPV. The sensitivity was similar between the HEP and ICU-4Ts score. CONCLUSIONS: The ICU-4Ts score better predicted the diagnosis of HIT compared to the 4Ts score. Prospective validation studies are needed to confirm these results.

Difficulties Detecting Clinically Relevant Factor Xa Inhibitor Levels Prior to Reversal With Andexanet Alfa for Intracranial Hemorrhage.

Coagulation factor Xa (recombinant), inactivated-zhzo (andexanet alfa) is approved for reversal of life-threatening bleeding with rivaroxaban and apixaban use. Clinical decision-making to initiate reversal is reliant on dose taken and timing of last dose. In practice, timing of last dose may be unknown, and the turnaround time for drug-specific anti-factor Xa levels at some institutions may be prolonged, leaving clinicians balancing a difficult decision with limited tools. This report includes a series of 3 patients who presented to our institution with an intracranial hemorrhage and received andexanet alfa for apixaban reversal. These cases highlight the challenges clinicians are facing when using andexanet alfa for emergent rivaroxaban or apixaban reversal when the timing of last dose is unknown, or patients fall outside of the recommended timeframe for use and clinically relevant drug levels are still suspected. Based on our experiences, we encourage other institutions to evaluate their abilities to rapidly and accurately detect the presence of clinically relevant rivaroxaban and apixaban levels when utilizing andexanet alfa.

Major Bleeding and Thrombosis Events in COVID-19 Versus Influenza Patients Requiring Extracorporeal Membrane Oxygenation.

Initial reports described a hypercoagulable state and an increased risk of thrombosis in patients who tested positive for SARS-CoV-2. Infected patients with severe acute respiratory distress syndrome in the setting of coronavirus disease 2019 (COVID-19) may require extracorporeal membrane oxygenation (ECMO), leading to coagulopathies and further increasing the risk for bleeding and thrombosis. We conducted a single-center retrospective cohort study to compare the incidence of major bleeding and thrombosis in COVID-19 versus influenza-positive patients requiring ECMO. There was no difference in the incidence of major bleeding (67.7% vs. 85.7%, p = 0.287) or major thrombosis (9.7% vs. 21.4%, p = 0.356) between COVID-19 and influenza patients, respectively. COVID-19 patients experienced significantly fewer major bleeding events per ECMO days compared with influenza (0.1 [interquartile range 0-0.2] vs. 0.2 [interquartile range 0.1-0.5], p = 0.026). Influenza patients may be at higher risk for developing coagulopathies that contribute to bleeding. Larger evaluations are needed to confirm these results and further assess bleeding and thrombosis risk in these populations.

Accuracy and safety of medication histories obtained at the time of intensive care unit admission of delirious or mechanically ventilated patients.

PURPOSE: Obtaining an accurate medication history from patients on hospital admission is a priority in pharmacy practice. Timely and accurate histories are imperative as they may help determine the etiology of illness and prevent medication errors. We conducted a quality improvement project to assess the accuracy of alternate-source medication histories obtained for critically ill patients who were delirious or mechanically ventilated at the time of intensive care unit admission. METHODS: Included patients were 18 years of age or older, admitted to the medical intensive care unit from August 2017 through January 2018, and had a medication history obtained from a family member or outpatient pharmacy due to active delirium or mechanical ventilation. Patients were directly interviewed after resolution of delirium or extubation. Discrepancies between the initial and follow-up histories were documented and categorized using the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index for Categorizing Medication Errors. RESULTS: Forty patients were included. One hundred four discrepancies were documented, with a median of 2 discrepancies per patient. The most common types of discrepancies were addition (51.9%), followed by omission (24.0%). NCC MERP index category A (51%) was the most common error classification identified. CONCLUSION: Discrepancies between initial and follow-up medication histories occurred at a frequent rate in delirious or mechanically ventilated patients; however, these discrepancies tended to be of low risk severity.

Evaluation of 4Ts score inter-rater agreement in patients undergoing evaluation for heparin-induced thrombocytopenia.

The American Society of Hematology and American College of Chest Physicians heparin-induced thrombocytopenia guidelines recommend calculation of a pretest probability score prior to performing laboratory testing, and the 4Ts score is commonly used. Inter-rater agreement of the 4Ts score has been evaluated, but limited data are available regarding the reliability of the 4Ts score when performed by nonexpert clinicians. The purpose of this study was to Compare 4Ts scores calculated by medical teams to an expert. A single-center observational study was conducted in patients evaluated for heparin-induced thrombocytopenia over 24 months. The primary outcome was difference in mean 4Ts score calculated by the medical team compared with an expert. Secondary outcomes included inter-rater agreement in risk category assignment and the negative predictive value (NPV) of the 4Ts score. The mean total 4Ts score was significantly higher when calculated by the medical team compared with expert (4.16 ±â€Š1.41 versus 3.42 ±â€Š1.53; P < 0.001). There was slight agreement in risk category assignment (Cohen κ coefficient = 0.164; P = 0.005). The NPV of the 4Ts score was 0.949 (95% confidence interval 0.891-1.000) when calculated by the medical team and 0.927 (95% confidence interval 0.869-0.984) when calculated by expert. Total 4Ts scores calculated by the medical team were significantly higher with only slight inter-rater agreement compared with expert. The NPV of the 4Ts score when calculated by nonexperts may be lower than previously reported. The recommendation to forgo laboratory testing for low 4Ts score patients may need to be revisited.

Minimizing cost associated with management of heparin-induced thrombocytopenia: A cost analysis of various laboratory testing models.

INTRODUCTION: Management of patients with suspected heparin-induced thrombocytopenia (HIT) can lead to significant costs. Reported cost-saving initiatives have focused on minimizing inappropriate testing in low-risk patients and optimizing alternative anticoagulant selection. We sought to further investigate how utilizing various HIT laboratory testing models would impact total cost of testing and alternative anticoagulant use. METHODS: Utilizing a retrospective cohort of adult patients tested for HIT over three years within our institution, we evaluated how utilization of four distinct laboratory models impacted total number of HIT test combinations completed, time to HIT testing finalization, percentage of patients discharged from the hospital prior to HIT testing finalization, total alternative anticoagulant days, and total anticipated major bleed events. Additionally, we calculated cost of laboratory testing and alternative anticoagulant associated with each model. RESULTS: A total of 482 patients were included in our cohort. A laboratory testing model that utilized an in-house platelet factor 4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA) completed three days weekly, and reflex serotonin release assay (SRA) with a five-day turnaround resulted in the shortest mean time to HIT testing finalization, lowest percentage of patients discharged prior to HIT testing finalization, and lowest total alternative anticoagulant days. CONCLUSIONS: Institutions should evaluate current HIT laboratory testing practices and assess for opportunities for optimization. Testing models utilizing a PF4-heparin antibody ELISA with a reflex SRA for positive results may improve testing metrics and lead to lower utilization of alternative anticoagulants.

Impact of a multidisciplinary workflow on safety and management of patients with heparin-induced thrombocytopenia.

PURPOSE: Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin administration. Management strategies are complex and include discontinuing heparin products, initiating alternative anticoagulants, interpreting laboratory test results, documenting heparin allergies, and providing patient education. Medication error reports and a retrospective review conducted at an academic medical center revealed an opportunity for a quality improvement initiative and led to the creation of a multidisciplinary workflow for the management of HIT. In a pre-post study, the impact of the multidisciplinary workflow on the safety and management of HIT was evaluated. METHODS: The preimplementation group consisted of adult patients tested for suspected HIT from April 4, 2014, through May 31, 2016; the postimplementation group consisted of adult patients tested from November 1, 2016, through October 31, 2018. The primary outcome was the incidence of heparin product administration while HIT testing was ongoing. The secondary outcome was the rate of appropriate heparin allergy documentation. RESULTS: The incidence of heparin product administration while HIT testing results were pending was significantly reduced, from 54.2% to 20.0% (P < 0.001), after workflow implementation. The rate of appropriate heparin allergy documentation significantly increased, from 95.0% to 100% (P < 0.001). CONCLUSION: Implementation of a multidisciplinary workflow for the management of HIT significantly reduced the incidence of heparin administration while testing was ongoing and improved the rate of appropriate heparin allergy documentation.

Safety and Efficacy of High-Dose Unfractionated Heparin Versus High-Dose Enoxaparin for Venous Thromboembolism Prevention in Morbidly Obese Hospitalized Patients.

BACKGROUND: Venous thromboembolism is a cause of morbidity and mortality in hospitalized patients, and morbid obesity increases this risk. Various prophylaxis dosing strategies have been investigated. However, it is unclear if high-fixed dose enoxaparin or high-fixed dose unfractionated heparin thromboprophylaxis is optimal for minimizing the incidence of major bleeding and reducing hospital-acquired venous thromboembolism. METHODS: A single-center retrospective observational study was conducted in hospitalized patients who were morbidly obese (body mass index ≥40 kg/m2) and who received either high-fixed dose enoxaparin (40 mg every 12 hours) or unfractionated heparin (7500 units every 8 hours) for venous thromboembolism prophylaxis. Co-primary outcomes included incidence of major bleeding and venous thromboembolism diagnosed during hospitalization. Predictors of major bleeding were evaluated by multivariable regression. RESULTS: In the 305 patients included (n = 190 unfractionated heparin, n = 115 enoxaparin), the incidence of major bleeding was significantly higher in the unfractionated heparin group (odds ratio [OR] 1.85, 95% confidence interval [CI] 1.07-3.13; P = 0.025), with no significant difference in the incidence of venous thromboembolism diagnosed during hospitalization. The only independent predictors of major bleeding were intensive care acuity (OR 3.32, 95% CI 1.91-5.78; P <0.001) and selection of unfractionated heparin rather than enoxaparin for venous thromboembolism prophylaxis (OR 2.16, 95% CI 1.22-3.82; P = 0.008). CONCLUSION: High-fixed dose unfractionated heparin for venous thromboembolism prophylaxis may lead to a higher risk of major bleeding events compared with high-fixed dose enoxaparin in patients who are morbidly obese.