Ou, Narith N.

Axillary artery intra-aortic balloon pump (axIABP) placement has been implemented as a bridging solution before heart transplantation. This study evaluates complications associated with axIABP support and describes an approach to minimize adverse events. We previously described a percutaneous approach for axIABP placement. However, patients receiving axIABP between September 1, 2017, and September 26, 2019 (n = 32) demonstrated a high rate of balloon pump malfunction (8/32; 25%) and other complications (totaling 15/32; 47%). Sixty-four patients were sequentially treated under a revised protocol. Compared to the initial cohort, no significant differences in demographics were noted. A significant reduction in rate of balloon malfunction (8/32, 25% vs. 1/64, 2%; p < 0.001) and total complications (15/32, 47% vs. 10/64, 16%; p = 0.0025) during the period of support were noted after intervention. Subsequent analysis of total complications per device size (40 vs. ≤ 34 ml balloon) revealed significantly reduced complications in patients with smaller devices (40% vs. 13%, respectively; p = 0.0022). This study provides guidelines to limit complications in patients supported with axIABP, facilitating a protracted period of bridging support.

ImportanceDirect oral anticoagulant (DOAC)–associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.ObjectiveTo evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.Data SourcesPubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.Study SelectionThe eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.Data Extraction and SynthesisPreferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.Main Outcomes and MeasuresThe primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.ResultsA total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.Conclusions and RelevanceIn the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Introduction Bumetanide can induce generalized musculoskeletal pain when administered as a continuous infusion, an effect that may be underrecognized. The purpose of this case series is to educate health care providers about the incidence and presentation of pain associated with bumetanide infusions, adding to the existing literature describing this adverse event. Clinical Findings Of 40 critically ill patients, 15 (38%) had increased pain scores after initiation of a continuous infusion of bumetanide, with symptoms commonly occurring 12 to 24 hours after initiation of the infusion. Reported descriptions of the pain included generalized aching, soreness, burning, allodynia, headaches, and exacerbation of underlying pain in localized areas. Increases in patient-reported pain correlated directly with initiation of the continuous infusion of bumetanide. Diagnosis Four of the 15 bumetanide-associated pain events (27%) were recognized as such by the health care team. Interventions Bumetanide was promptly discontinued in the 4 identified cases. The 11 patients (73%) whose pain was not recognized as related to bumetanide remained on a continuous infusion of bumetanide and received pain medications including opioids. Infusions were stopped when patients transitioned to dialysis (n = 8 [53%]), began receiving comfort care (n = 5 [33%]), or completed diuresis therapy (n = 2 [13%]). Outcomes For all patients, pain symptoms resolved within 24 to 48 hours after discontinuation of bumetanide infusion with no significant electrolyte abnormalities. Conclusion Bumetanide-induced pain is more common than previously described. Early recognition of this adverse event can prevent patient discomfort and escalation of treatment.

AbstractBackgroundPolypharmacy in older adults leads to increased risks of side effects and drug‐drug interactions, affecting their health outcomes and quality of life. Deprescribing, the act of simplifying medication regimens, is challenging due to the lack of consensus guidelines.HypothesisTo offer some guidance on managing medication regimens for older cardiovascular patients.MethodsWe reviewed the most recent pertinent guidelines and literature.ResultsThis review provides practical considerations for appropriate prescribing in the older population with cardiovascular disease in order to strike a balance between unnecessary or harmful medications and therapies with proven long‐term benefits.ConclusionOn‐going dialogue between healthcare providers and patients allows close monitoring of medication effectiveness and prevention of side effects. Medication regimens require individualization, as patients' goals of care change with advancing age.

Controversy exists regarding the use of dose capping of weight-based unfractionated heparin (UFH) infusions in obese and morbidly obese patients. The primary objective of this study was to compare time to first therapeutic activated partial thromboplastin time (aPTT) in hospitalized patients receiving UFH for acute venous thromboembolism (VTE) among three body mass index (BMI) cohorts: non-obese (< 30 kg/m 2 ), obese (30–39.9 kg/m 2 ), and morbidly obese (⩾ 40 kg/m 2 ). In this single-center, retrospective cohort study, patients were included if they ⩾ 18 years of age, had a documented VTE, and were on an infusion of UFH for at least 24 hours. Weight-based UFH doses were calculated using actual body weight. A total of 423 patients met the inclusion criteria, with 230 (54.4%), 146 (34.5%), and 47 (11.1%) patients in the non-obese, obese, and morbidly obese cohorts, respectively. Median times to therapeutic aPTT were 16.4, 16.6, and 17.1 hours in each cohort. Within 24 hours, the cumulative incidence rates for therapeutic aPTT were 70.7% for the non-obese group, 69.9% for the obese group, and 61.7% for the morbidly obese group (obese vs non-obese: HR = 1.02, 95% CI: 0.82–1.26, p = 0.88; morbidly obese vs non-obese: HR = 0.87, 95% CI: 0.62–1.21, p = 0.41). There was no significant difference in major bleeding events between BMI groups (obese vs non-obese, p = 0.91; morbidly obese vs non-obese, p = 0.98). Based on our study, heparin dosing based on actual body weight without a dose cap is safe and effective.

Abstract Background An increasing number of patients (pts) requiring anticoagulation are treated with oral factor Xa inhibitors (DOAC) as an alternative to vitamin K antagonists. Prior to the recent approval of coagulation factor Xa (recombinant), inactivated-zhzo in May 2018, four factor prothrombin complex concentrates (4PCC) have been used to reverse the effects of DOACs. We retrospectively analyzed our institutional experience with 4 PCC for reversal of apixaban and rivaroxaban to determine the indications for 4PCC use and outcomes. Methods After IRB approval, pts receiving 4PCC, from Feb 2016 to January 2018 were identified from our pharmacy database and pts receiving PCC for reversal of apixiban and rivaroxaban were selected. Consenting pts medical records (MR) were reviewed for demographics and indications for DOAC and 4PCC as well as outcomes of 4PCC use. Pts were excluded if they had discontinued DOAC greater than 7 days before receiving 4PCC or if they were started on alternative forms of anticoagulation at a therapeutic dose prior to receiving PCC. Primary endpoint was clinical efficacy (clinical improvement or stability) or ability to undergo required procedure) and secondary endpoint was safety (thromboembolism and death) up to 35 days post-infusion of 4PCC. Stability for intracranial hemorrhages (ICH) was determined by clinical improvement and if head imaging performed, no change in head CT or MRI scan, whereas stability for other bleeds was determined by hemoglobin stability and opinions of providers in the MR. Primary efficacy outcome for pts undergoing surgery was based on MR comments by the performing surgeon and use of other hemostatic agents and red blood cell transfusions. Results 49 (32 male) pts, median age of 74 (31-95) years, met our study criteria and received 4PCC for reversal of apixaban (n=29) and rivaroxaban (n=20). Indications for anticoagulation were atrial fibrillation (n=35) and thrombosis (n=14). Of the 14 pts with thrombosis, 11 had deep vein thrombosis while 3 had thrombosis at other sites (arterial graft thrombus, aortic thrombus, and portal vein thrombosis). 4PCC was administered in the emergency department (n=36), intensive care unit (n=10), or the general medical wards (n=3). Indications for 4PCC included bleeding (n=40), procedure/surgery (n=6), and hemodynamic instability with clinical suspicion for bleeding (n=3). Bleeding location is reported in table 1. All procedure/surgery performed for clinical symptoms not related to hemorrhage were non-elective procedures and included exploratory laparotomy (n=4), laparoscopic cholecystectomy (n=1), and incision and drainage of abdominal wall abscess (n=1). Median PCC dose was 42 (10.3-63.3) IU/kg. Outcomes 32/40 (80%) pts had stability or an improvement in bleeding, while 5 pts had bleeding that did not improve. 3 pts, all with ICH, had a bleed that worsened 8 (6-8) hours after PCC but then spontaneously stabilized 24 (8-24) hours later. Of those presenting with clinical bleeding, 3 pts received FFP within 3 hours prior to treatment with 4PCC, 2 pts received FFP within 12 hours after 4PCC, and 2 pts received FFP within 3 hours before and 12 hours after 4PCC. Of 40 pts receiving PCC for bleeding, 14 also had a procedure to help achieve hemostasis (Table 2). All 6 pts were able to undergo procedure/surgery. 5/6 patients achieved adequate hemostasis. One pt had no mention of unanticipated bleeding in the MR but received 8 units of FFP intraoperatively after 4PCC. 6/49 (12%) pts had a thrombotic complication within 35 days of receiving PCC (median 4 days; (range 1-31) including arterial graft thrombus (n=1), superficial venous thrombus (n=1), bilateral soleal vein thrombosis (n=1), internal jugular vein and innominate vein thrombosis (n=1) stroke (n=1), and progression of preexisting portal vein thrombosis (n=1). All-cause mortality was 20%. 3/10 deaths were in pts who never achieved neurologic recovery after ICH and one pt had stroke-like symptoms leading to death 30 days after 4PCC (administered for ICH). Conclusion In this cohort, 80% of pts demonstrated clinical stability/improvement of hemorrhage. All pts were able to undergo surgical procedures; however 17% required additional FFP to achieve hemostasis. Thromboembolism occurred in 12% of patients. No deaths could definitely be attributed to 4PCC; however, 30% of deaths could be attributable to the underlying hemorrhagic episode. Disclosures No relevant conflicts of interest to declare.

Introduction Safe management of warfarin in the inpatient setting can be challenging. At the Mayo Clinic hospitals in Rochester, Minnesota, we set out to improve the safety of warfarin management among surgical and non-surgical inpatients. Methods A multidisciplinary team designed a pharmacist-managed warfarin protocol (PMWP) which designated warfarin dosing to inpatient pharmacists with guidance from computerised dosing algorithms. Ordering this protocol was ultimately designed as an ‘opt out’ practice. The primary improvement measure was frequency of international normalised ratio (INR) greater than 5; secondary measures included adoption rate of the protocol, a counterbalance INR metric (INR <1.7 three days after first inpatient warfarin dose), and complication rates, including bleeding and thrombosis events. An interrupted time series analysis was conducted to compare outcomes. Results Among over 50 000 inpatient warfarin recipients, the PMWP was adopted for the majority of both surgical and non-surgical inpatients during the study period (1 January 2005 to 31 December 2011). The primary improvement measure decreased from 5.6% to 3.4% for medical patients and from 5.2% to 2.4% for surgical patients during the preimplementation and postimplementation periods, respectively. The INR counterbalance measure did not change. Postoperative bleeding decreased from 13.5% to 11.1% among surgical patients, but bleeding was unchanged among medical patients. Conclusion Our PMWP led to achievement of improved INR control for inpatient warfarin recipients and to less near-term bleeding among higher risk, surgical patients.

To reliably assess quality, a standardized electronic approach is needed to identify bleeding events. The study aims were the following: (1) clinically validate an electronic health record–based algorithm for bleeding and (2) assess interrater results to determine validity and reliability. Data were analyzed before and after implementation of a pharmacist-managed warfarin protocol. Bleeding was based on ≥2 of 3 criteria: (1) diagnosis indicating bleeding, (2) lab value decrease suggesting bleeding, and (3) blood product use. All suspected bleeds (234) and a sample (58) not meeting criteria were compared with clinical review. There were 234 bleeding cases identified electronically. Reviewer agreement was 78.2% (κ = 0.565). Algorithm sensitivity was 93.9% and positive predictive value 46.2%. Algorithm identification was least accurate for those with only 2 criteria but good for those with all criteria. This study supports using multiple electronic criteria to identify bleeding events. However, cases having exactly 2 criteria may require manual review for validation.