Emergent Reversal of Antithrombotics and Treatment of Life-Threatening Bleeding from Coagulopathies: A Clinical Review.

BACKGROUND: Reversal of antithrombotic agents and treatment of life-threatening bleeding episodes from coagulopathies can be a stressful scenario for clinicians, especially when the selection of treatment options should occur quickly. Understanding the options available for these agents requires emergency physicians to be familiar with the current data surrounding new therapies and dosing strategies for the treatment of bleeding from reversible and nonreversible antithrombotics and coagulopathic conditions. OBJECTIVE: To provide quick resource guides for the reversal of major or life-threatening bleeding caused by antithrombotic agents or in the setting of coagulopathies. METHODS: A literature search for articles published through September 2021 related to antithrombotic reversal and treatment of acute bleeding from coagulopathies was conducted using the PubMed clinical database. Selected articles were used to generate 5 guidance tables in this clinical review. DISCUSSION: Four guidance tables for how to treat major or life-threatening bleeding from antithrombotic agents and 1 table for how to manage life-threatening bleeding for coagulopathies are presented as a quick reference tool for the emergency physician. Additional information on upcoming reversal agents and possible treatment options are provided herein. CONCLUSIONS: In this clinical review, a series of 5 tables were created to provide quick and comprehensive guidance for the emergency physician when treating major or life-threatening bleeding caused by antithrombotic agents or coagulopathies. © 2022 Elsevier Inc.

Electronic clinical decision support to facilitate a change in clinical practice: Small details can make or break success.

BACKGROUND: The use of electronic clinical decision support (CDS) is becoming common to change historically common clinical practices considered outdated by current guidelines. Preimplementation design of CDS tools is key to their success in changing clinical behaviors. Unfortunately, there are no established protocols for CDS tool development, and CDS failure can result from even small design flaws. This paper describes an example of a design oversight and how correction resulted in CDS success. STUDY DESIGN AND METHODS: We performed a retrospective review of compliance with a CDS tool to encourage the use of prothrombin complex concentrate over plasma transfusion for the emergent reversal of warfarin. We identified a potential design flaw, made the necessary modifications, and repeated the compliance review. RESULTS: After CDS, plasma orders declined by 150 units/mo; however, 48% of orders placed for non-warfarin coagulopathy were still for warfarin reversal. Hospital-wide, this noncompliance was 36% and was 80% in the emergency department. By simply relocating the qualifier "NOT on warfarin" from the end to the beginning of the order, noncompliance for warfarin reversal was reduced to 5% (P < .0001 by chi-square). CONCLUSIONS: The successful use of electronic clinical decision support in the electronic medical record can depend on optimal design. Missing even small design elements such as the positioning of key terms within the tool can result in an ineffective CDS. Important design strategies to avoid poor performance are discussed as they relate to the CDS tool we describe.

Correction to: Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

The authors note that there is a discrepancy between the text of the paper and Table 2 regarding physician subspecialty certification requirements in neurocritical care for Level II centers.

Outcomes of red blood cell transfusions prescribed in organ donors by the Digital Intern, an electronic decision support algorithm.

BACKGROUND: The Digital Intern (DI) is an electronic decision support tool for the management of organ donors. One algorithm determines the dose, in units of red blood cells to be transfused, based on hematocrit (Hct) thresholds and targets. The effectiveness of the transfusion dose calculated by the DI in terms of achieving the selected Hct target and the duration of the targeted dose is not known. STUDY DESIGN AND METHODS: This was a retrospective study to describe the outcomes of transfusions prescribed by the DI. Pre- and posttransfusion Hct levels were compared to define response and all posttransfusion Hct values were plotted to evaluate the duration of the prescribed dose. RESULTS: A total of 120 organ donors were studied and 22 donors had 28 transfusions (six were transfused twice). The transfused donors were a mix of trauma and medical admissions and brain death and cardiac death donors. The transfusion target of 24% Hct was attained in 96% of transfusions. The mean number of units transfused was 1.4 and the mean time from transfusion to procurement was 19.8 hours. There was a decline in Hct over time after transfusion in all but one case with a mean decline of 1.9% Hct over 13 hours. Six donors were transfused twice, likely due to a longer donor time period (41.7 hr vs. 27 hr). CONCLUSIONS: The DI provided transfusion dosing that achieved the desired threshold in the majority of organ donors transfused. Ongoing work focuses on application of this technology to transfusions in general patient populations.

The blood utilization calculator, a target-based electronic decision support algorithm, increases the use of single-unit transfusions in a large academic medical center.

BACKGROUND: Electronic decision support has been used to reduce use of red blood cell (RBC) transfusion. With the goal of reducing transfusions, we modified our RBC orders to default to 1 unit. Next, we created a target-based algorithm, the blood utilization calculator or BUC, to calculate a dose in units, based on initial hemoglobin or hematocrit and weight. STUDY DESIGN AND METHODS: RBC orders defaulted to 1 unit in March 2016 and the BUC was implemented in July 2016. This gave three periods to compare old orders (before intervention), new orders (1-unit default), and the BUC period. A hospital dashboard that tracks blood product orders was queried to determine changes in single-unit transfusions between periods. Changes in transfusions were compared by analysis of variance. Acceptance of the BUC dosage recommendation was studied in both medical-based and surgical-based specialties. RESULTS: The number of single-unit transfusions showed significant increases after each of the two interventions studied from 247 ± 19 before interventions to 358 ± 19 and then to 445 ± 141-unit transfusions/month (p < 0.0001). The ratio of 1-unit to 2-unit transfusions increased from 0.72 to 1.67 (p < 0.0001) and we observed a 19% overall reduction in units transfused. The BUC recommendation was accepted in 49% of orders. CONCLUSIONS: One-unit default orders and implementation of the BUC resulted in a significant increase in the use of single-unit transfusions. Improvement in the rate of acceptance of the BUC recommendation should further increase the use of single-unit transfusions.

Standards for Neurologic Critical Care Units: A Statement for Healthcare Professionals from The Neurocritical Care Society.

Neurocritical care is a distinct subspecialty focusing on the optimal management of acutely ill patients with life-threatening neurologic and neurosurgical disease or with life-threatening neurologic manifestations of systemic disease. Care by expert healthcare providers to optimize neurologic recovery is necessary. Given the lack of an organizational framework and criteria for the development and maintenance of neurological critical care units (NCCUs), this document is put forth by the Neurocritical Care Society (NCS). Recommended organizational structure, personnel and processes necessary to develop a successful neurocritical care program are outlined. Methods: Under the direction of NCS Executive Leadership, a multidisciplinary writing group of NCS members was formed. After an iterative process, a framework was proposed and approved by members of the writing group. A draft was then written, which was reviewed by the NCS Quality Committee and NCS Guidelines Committee, members at large, and posted for public comment. Feedback was formally collated, reviewed and incorporated into the final document which was subsequently approved by the NCS Board of Directors.

Standardization of transfusion practice in organ donors using the Digital Intern, an electronic decision support algorithm.

BACKGROUND: Prospective clinical trials support restrictive thresholds for red blood cell (RBC) transfusion. Nonsurvivable donors are a major source of organs for transplantation. The Digital Intern (DI) is a computer algorithm to standardize donor care that includes a more restrictive transfusion threshold. The impact of standardized and restrictive RBC transfusion in organ donors, as determined by the DI, has not been reported. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study to compare the transfusion practice of the DI (n = 100) to a historic group of physician-managed donors (n = 90). Transfusion rates, the number of units transfused, and pretransfusion laboratory values were compared between groups. The variability of these parameters was also compared between groups. Finally, the number of transplanted organs per donor in each group was compared. RESULTS: The mean time as a donor was 25.9 ± 15.2 hours and was not different between the groups. In the DI group 19% were transfused compared to 26% in the control group (p = 0.3). The number of units transfused was less in the DI group (1 unit vs. 2 units per transfusion, p = 0.03) and the pretransfusion hematocrit was lower in the DI group (23% vs. 27%, p = 0.01). The variability in the latter two parameters was significantly lower in the DI group. The number of transplanted organs per donor was similar in both groups (3.24 [DI] vs. 3.03 [control], p = 0.37). CONCLUSION: The DI provides a more standardization transfusion practice in organ donors and reduces blood use without compromising transplantable organs.

Use of High-Flow Continuous Renal Replacement Therapy with Citrate Anticoagulation to Control Intracranial Pressure by Maintaining Hypernatremia in a Patient with Acute Brain Injury and Renal Failure.

Traumatic brain injury and intracranial hypertension often require treatment to optimize patient outcome. There are a variety of complex medical conditions that can preclude standard approaches to the treatment of intracranial hypertension. We describe a case where a novel approach using continuous dialysis with trisodium citrate was used to optimize the outcome of a young male with acute renal failure and acute respiratory distress syndrome in the setting of acute traumatic brain injury.

The emergent reversal of coagulopathies encountered in neurosurgery and neurology: a technical note.

It is imperative for neurologists, neurosurgeons, and neurointensivists to know how to stop life-threatening hemorrhage in both surgical and non-surgical patients. However, knowing how to medically correct a coagulopathy has become increasingly challenging as more contemporary and sophisticated anticoagulation agents are developed and prescribed. In a time-sensitive and life-threatening situation, where there is little margin for error, the neurosurgeon may not have ready access to information about the drug or condition that caused the coagulopathy or the information on how to treat it. This thorough review of the literature provides a comprehensive overview of the medications and conditions that can lead to persistent and/or life-threatening intracranial hemorrhage.

Safety of a DVT chemoprophylaxis protocol following traumatic brain injury: a single center quality improvement initiative.

BACKGROUND: Venous thromboembolism (VTE) is a complication that affects approximately 30 % of moderate and severe traumatic brain injury (TBI) patients when pharmacologic prophylaxis is not used. Following TBI, specifically in the case of contusions, the safety and efficacy of pharmacologic thromboembolism prophylaxis (PTP) has been studied only in small sample sizes. In this study, we attempt to assess the safety and efficacy of a PTP protocol for TBI patients, as a quality improvement (QI) initiative, in the neuroscience intensive care unit (NSICU). METHODS: Between January 1st and December 31st, 2009, consecutive patients discharged from the University of Wisconsin NSICU after >a 48 h minimum stay were evaluated as part of a QI project. A protocol for the initiation of PTP was designed and implemented for NSICU patients. The protocol did not vary based on type of intracranial injury. The rate of VTE was reported as was heparin-induced thrombocytopenia and PTP-related expansion of intracranial hemorrhage (IH) requiring reoperation. The number of patients receiving PTP and the timing of therapy were tracked. Patients were excluded for persistent coagulopathy, other organ system bleeding (such as the gastrointestinal tract), or pregnancy. Faculty could opt out of the protocol without reason. Using the same criteria, patients discharged during the preceding 6 months, from July 1st to December 31st, 2008, were evaluated as controls as the PTP protocol was not in effect during this time. RESULTS: During the control period, there were 48 head trauma admissions who met the inclusion criteria. In 22 patients (45.8 %), PTP was initiated at an average of 4.9 ± 5.4 days after admission. During the protocol period, there were 87 head trauma admissions taken from 1,143 total NSICU stays who met criteria. In 63 patients (72.4 %), the care team in the NSICU successfully initiated PTP, at an average of 3.4 ± 2.8 days after admission. All 87 trauma patients were analyzed, and the rate of clinically significant deep venous thrombosis (DVT) was 6.9 % (6 of 87). Three protocol patients (3.45 %) went to the operating room for surgery after the initiation of PTP; none of these patients had a measurable change in hemorrhage size on head CT. The change in percentage of patients receiving PTP was significantly increased by the protocol (p < 0.0001); while the average days to first PTP dose trended down with institution of the protocol, this change was not statistically significant. CONCLUSION: A PTP protocol in the NSICU is useful in controlling the number of complications from DVT and pulmonary embolism while avoiding additional IH. This protocol, based on a published body of literature, allowed for VTE rates similar to published rates, while having no PTP-related hemorrhage expansion. The protocol significantly changed physician behavior, increasing the percentage of patients receiving PTP during their hospitalization; whether long-term patient outcomes are affected is a potential goal for future study.

Evaluation of an adaptive, rule-based dosing algorithm to maintain therapeutic anticoagulation during atrial fibrillation ablation.

Background: Cerebral thromboembolism during atrial fibrillation (AF) ablation is an infrequent (0.17%) complication in part owing to strict adherence to intraprocedural anticoagulation. Failure to maintain therapeutic anticoagulation can lead to an increase in events, including silent cerebral ischemia. Objective: To evaluate a computerized, clinical decision support system (CDSS) to dose intraprocedural anticoagulation and determine if it leads to improved intraprocedural anticoagulation outcomes during AF ablation. Methods: The Digital Intern dosing algorithm is an adaptive, rule-based CDSS for heparin dosing. The initial dose is calculated from the patient's weight, baseline activated clotting time (ACT), and outpatient anticoagulant. Subsequent recommendations adapt based on individual patient ACT changes. Outcomes from 50 cases prior to algorithm introduction were compared to 139 cases using the algorithm. Results: Procedures using the dosing algorithm reached goal ACT (over 300 seconds) faster (17.6 ± 11.1 minutes vs 33.3 ± 23.6 minutes pre-algorithm, P < .001). ACTs fell below goal while in the LA (odds ratio 0.20 [0.10-0.39], P < .001) and rose above 400 seconds less frequently (odds ratio 0.21 [0.07-0.59], P = .003). System Usability Scale scores were excellent (96 ± 5, n = 7, score >80.3 excellent). Preprocedure anticoagulant, weight, baseline ACT, age, sex, and renal function were potential predictors of heparin dose to achieve ACT >300 seconds and final infusion rate. Conclusion: A heparin dosing CDSS based on rules and adaptation to individual patient response improved maintenance of therapeutic ACT during AF ablation and was rated highly by nurses for usability.

Effect of risk, expectancy, and trust on clinicians' intent to use an artificial intelligence system -- Blood Utilization Calculator.

A gap exists between the capabilities of artificial intelligence (AI) technologies in healthcare and the extent to which clinicians are willing to adopt these systems. Our study addressed this gap by leveraging 'expectancy-value theory' and 'modified extended unified theory of acceptance and use of technology' to understand why clinicians may be willing or unwilling to adopt AI systems. The study looked at the 'expectancy,' 'trust,' and 'perceptions' of clinicians related to their intention of using an AI-based decision support system known as the Blood Utilization Calculator (BUC). The study used purposive sampling to recruit BUC users and administered a validated online survey from a large hospital system in the Midwest in 2021. The findings captured the significant effect of 'perceived risk' (negatively) and 'expectancy' (positively) on clinicians' 'trust' in BUC. 'Trust' was also found to mediate the relationship of 'perceived risk' and 'expectancy' with the 'intent to use BUC.' The study's findings established pathways for future research and have implications on factors influencing BUC use.

Clinicians' Perceptions of an Artificial Intelligence-Based Blood Utilization Calculator: Qualitative Exploratory Study.

BACKGROUND: According to the US Food and Drug Administration Center for Biologics Evaluation and Research, health care systems have been experiencing blood transfusion overuse. To minimize the overuse of blood product transfusions, a proprietary artificial intelligence (AI)-based blood utilization calculator (BUC) was developed and integrated into a US hospital's electronic health record. Despite the promising performance of the BUC, this technology remains underused in the clinical setting. OBJECTIVE: This study aims to explore how clinicians perceived this AI-based decision support system and, consequently, understand the factors hindering BUC use. METHODS: We interviewed 10 clinicians (BUC users) until the data saturation point was reached. The interviews were conducted over a web-based platform and were recorded. The audiovisual recordings were then anonymously transcribed verbatim. We used an inductive-deductive thematic analysis to analyze the transcripts, which involved applying predetermined themes to the data (deductive) and consecutively identifying new themes as they emerged in the data (inductive). RESULTS: We identified the following two themes: (1) workload and usability and (2) clinical decision-making. Clinicians acknowledged the ease of use and usefulness of the BUC for the general inpatient population. The clinicians also found the BUC to be useful in making decisions related to blood transfusion. However, some clinicians found the technology to be confusing due to inconsistent automation across different blood work processes. CONCLUSIONS: This study highlights that analytical efficacy alone does not ensure technology use or acceptance. The overall system's design, user perception, and users' knowledge of the technology are equally important and necessary (limitations, functionality, purpose, and scope). Therefore, the effective integration of AI-based decision support systems, such as the BUC, mandates multidisciplinary engagement, ensuring the adequate initial and recurrent training of AI users while maintaining high analytical efficacy and validity. As a final takeaway, the design of AI systems that are made to perform specific tasks must be self-explanatory, so that the users can easily understand how and when to use the technology. Using any technology on a population for whom it was not initially designed will hinder user perception and the technology's use.

Cerebellar hemorrhage as a first presentation of acquired Hemophilia A.

BACKGROUND: Acquired hemophilia A (AHA) is an uncommon coagulation disorder caused by the development of autoantibodies against coagulation factor VIII (FVIII). While intracranial hemorrhage is a known complication of AHA, intracranial hemorrhage as the presenting manifestation of AHA has only been described in three previous case reports. METHOD: We report a case of an 86-year-old woman with no previously reported history of coagulopathy presenting with an acute intraparenchymal cerebellar hemorrhage and laboratory studies demonstrating an isolated prolonged activated partial thromboplastin time (aPTT). We discuss an approach to the prolonged aPTT, and review the literature concerning the diagnosis and treatment of AHA. RESULTS: Occipital decompressive craniectomy with evacuation of the hemorrhage was performed. Eight hours following the procedure, the patient's status acutely declined with demonstration of a reoccurrence of the cerebellar hemorrhage and new right frontal lobe hemorrhage. After discussion with the patient's family, life-sustaining support measures were withdrawn. Postmortem analysis revealed a low FVIII activity level and the presence of FVIII inhibitor. CONCLUSION: The presentation of intracranial hemorrhage with an isolated prolonged aPTT is concerning for an acquired hemophilia with FVIII deficiency. Other causes of isolated prolonged aPTT such as a lupus anticoagulant must also be considered. Preoperative identification and work-up of the coagulation abnormality is essential to guide initial treatment.

Ventriculoperitoneal Shunt Drainage Increases With Gravity and Cerebrospinal Fluid Pressure Pulsations: Benchtop Model.

BACKGROUND: There have been few improvements in cerebrospinal fluid (CSF) shunt technology since John Holter introduced the silicon valve, with overdrainage remaining a major source of complications. OBJECTIVE: To better understand why valves are afflicted by supra-normal CSF flow rates. We present in Vitro benchtop analyses of flow through a differential pressure valve under simulated physiological conditions. METHODS: The pseudo-ventricle benchtop valve testing platform that comprises a rigid pseudo-ventricle, compliance chamber, pulsation generator, and pressure sensors was used to measure flow rates through a differential pressure shunt valve under the following simulated physiological conditions: orientation (horizontal/vertical), compliance (low/medium/high), and pulsation generator force (low/medium/high). RESULTS: Our data show that pulse pressures are faithfully transmitted from the ventricle to the valve, that lower compliance and higher pulse generator forces lead to higher pulse pressures in the pseudo-ventricle, and that both gravity and higher pulse pressure lead to higher flow rates. The presence of a valve mitigates but does not eliminate these higher flow rates. CONCLUSION: Shunt valves are prone to gravity-dependent overdrainage, which has motivated the development of gravitational valves and antisiphon devices. This study shows that overdrainage is not limited to the vertical position but that pulse pressures that simulate rhythmic (eg, cardiac) and provoked (eg, Valsalva) physiological CSF pulsations increase outflow in both the horizontal and vertical positions and are dependent on compliance. A deeper understanding of the physiological parameters that affect intracranial pressure and flow through shunt systems is prerequisite to the development of novel valves.

Stability of Sodium Nitroprusside and Sodium Thiosulfate 1:10 Intravenous Admixture.

PURPOSE: Thiosulfate has been shown to reduce the risk of cyanide toxicity during nitroprusside administration. Admixtures containing both agents may provide a safe and effective alternative to more expensive agents used to reduce blood pressure in the critically ill patient. This study determined the physical and chemical stability of a 1:10 nitroprusside:thiosulfate admixture, stored up to 48 hours. The economic consequences of a shift toward using thiosulfate and nitroprusside, and away from higher cost alternatives, are considered. METHODS: Seven samples of 50 mg nitroprusside and 500 mg thiosulfate were prepared and stored away from light, at room temperature, and in a refrigerator prepared in D5W and NS. Each sample was analyzed via a novel high-performance liquid chromatographic (HPLC) method at time 0, 8, 24, and 48 hours. The method was tested and passed specifications for linearity, reproducibility, and accuracy. A visual inspection by 9 licensed pharmacists was used to demonstrate physical stability. A cost evaluation comparing nitroprusside and thiosulfate to alternative agents was completed. RESULTS: The concentration of both nitroprusside and thiosulfate remain greater than 95% of the initial concentration through 48 hours. Physical compatibility was confirmed in all samples tested through 72 hours. CONCLUSION: The combination of nitroprusside and thiosulfate is chemically and physically stable as a single compounded dose for up to 48 hours when stored at room temperature and protected from light. The admixture represents an inexpensive option to other higher cost alternatives such as nicardipine or clevidipine.

Sulcal and gyral anatomy of the orbitofrontal cortex in relation to the recurrent artery of Heubner: an anatomical study.

The aim of this study is to investigate the sulcal and the gyral anatomy of the orbitofrontal cortex with its arterial supply. Ten gross formaline fixed adult brains (20 hemispheres) were used to show the gyral and sulcal anatomy of the inferior frontal lobe, and its arterial supply. The arteries were investigated with special attention to the relationship between the recurrent artery of Heubner (RAH) and the gyrus rectus (GR). Medial and lateral orbital sulci were connected in 4 right hemispheres, and in 7 of the left. The orbital sulci were connected with olfactory sulcus in one right hemispheres, but not in the left. In the right hemispheres, the RAH traveled across the GR in 7 hemispheres and looped over the posterior aspect of the GR in 3 hemispheres. In the left hemispheres, RAH crossed the GR in 8 and looped over the posterior aspect of the GR before entering the anterior perforating substance in 2 hemispheres. There are considerable variations among the gyri and sulci of the orbitofrontal cortex and it is difficult to describe a precise architectural pattern. The RAH demands special attention during GR resection in aneurysm surgery.

Intracranial Pressure Sensor and Valve to Control Hydrocephalus.

Hydrocephalus is a neurological condition that can result from trauma, hemorrhage, cancer, and infection. To control the intracranial pressure (ICP) a shunt is implanted to drain the cerebro-spinal fluid (CSF). We are working to develop an implantable pressure sensor. When the ICP is too high it will open a valve to relieve the ICP. When the ICP is too low, it will close the valve.