Remimazolam: A Retrospective Study of Initial Safety and Recovery Data in Diverse Procedural Sedation.

PURPOSE: The new ultra-short-acting benzodiazepine, remimazolam, offers a pharmacokinetic and pharmacodynamic advantage over commonly used procedural sedation medication. This retrospective study explored the real-world utilization of remimazolam during procedural sedation to support the development of a nurse sedation protocol. The primary outcome was to identify associations between recovery time, adverse reactions, and dose-response in expanded patient populations. METHODS: This study reviewed charts of 292 adult patients from 3 hospitals within one institution who received remimazolam during procedural sedation between June 1, 2021 and December 31, 2021. Data were analyzed using logistic and linear regression. FINDINGS: The median time to alert in patients receiving remimazolam alone was 12 minutes (interquartile range 10, 17) and increased when additional sedation medications were utilized. Receiving additional sedative medication significantly increased the odds of hypoxia (OR 2.77, 95% CI 1.30-5.91, P = 0.008) after adjusting for body mass index (BMI), American Society of Anesthesiologists physical status (ASA-PS), and total remimazolam dose. There was a 25% increase in odds of experiencing hypoxia for every 5 kg/m2 increase in BMI (95% CI 1.01-1.54, P = 0.037). IMPLICATIONS: Remimazolam presents as a promising option for nurse procedural sedation, offering minimal impact on hemodynamics and respirations, quick recovery, and no residual sedative effects.

Lymphatic Mapping with Contrast-enhanced Ultrasound for Lymphaticovenous Anastomosis Surgery: How We Do It.

Lymphaticovenous anastomosis (LVA) surgery is an effective surgery for the treatment of lymphedema in the extremities. Indocyanine green lymphography is the reference standard for visualizing lymphatics for LVA surgery, but it has several limitations; most notably, superficial dermal congestion can mask deeper lymphatic vessels. To overcome the limitations, we add contrast-enhanced ultrasound (CEUS) lymphography. We have previously reported that CEUS lymphography can identify lymphatic vessels for LVA surgery that indocyanine green lymphography does not. Here, we describe how we perform CEUS lymphography, including workflow, technique, and documentation. Before informed consent, the patient must be screened for possible adverse reactions to microbubbles. The procedure involves multiple intradermal injections of the microbubble agent at various sites along the extremity. After each injection, imaging for microbubble uptake by lymphatic vessels is performed using an ultrasound scanner with contrast-specific software. We use sulfur hexafluoride lipid-type A microspheres (Lumason/SonoVue; Bracco Suisse SA), but we are investigating the performance of other Food & Drug Administration-approved microbubble agents for CEUS lymphography. Having a systematic approach to marking the skin can mitigate the hindrance of marking over ultrasound coupling gel. Another benefit of CEUS lymphography is the rapid identification of neighboring veins compatible in size and location for anastomosis. We hold regular scheduled multidisciplinary meetings for coordination of care, discussion of outcomes, quality assurance, and ongoing innovation.

Activated Prothrombin Complex Concentrate in Pediatric Cardiac Patients, Our Early Experience.

BACKGROUND: Pediatric cardiac surgery is associated with abnormal coagulation, bleeding, and nearly ubiquitous transfusions. With the popularization of patient blood management, attempts are being made to decrease liberal transfusions by administering prothrombin complex concentrates (PCCs). The safety and efficacy of PCCs in adult cardiac surgery has been studied extensively, but only few reports address this in children. We performed an observational study focused on transfusion requirements after off-label use of activated PCC Factor Eight Inhibitor Bypassing Activity (FEIBA) as an adjunct to post-cardiopulmonary bypass (CPB) hemostatic protocol. METHODS: We reviewed the medical records of children ≤15 kg undergoing cardiac operations with CPB between May 2018 and March 2022. A propensity score (PS) analysis was performed to identify matched pairs of patients who did and did not receive FEIBA. RESULTS: Out of 210 patients who met the inclusion criteria, 44 patients received FEIBA. Propensity score-based analysis identified 40 matched pairs of patients with similar baseline characteristics. There was no statistically significant difference in the primary outcome-the volume of transfusion after CPB, which included all allogeneic blood products and salvaged washed red cells administered after protamine. Specifically, FEIBA patients were transfused 28 (22-34) mL/kg and controls were transfused 22 (11-49) mL/kg, P = .989. Upon arrival to ICU, the FEIBA group averaged an 8% lower international normalized ratio, compared with the controls (P = .009) and a 1.08 g/dL higher hemoglobin (P = .050). Neither difference remained significant on POD 1. CONCLUSIONS: In this exploratory study, we found no change in transfusion requirements after CPB despite FEIBA administration.

Evaluation of Direct Oral Anticoagulant Reversal Agents in Intracranial Hemorrhage: A Systematic Review and Meta-analysis.

Importance: Direct 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. Objective: To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. Data Sources: PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. Study Selection: The 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 Synthesis: Preferred 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 Measures: The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. Results: A 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 Relevance: In 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.

Twinkling-guided ultrasound detection of polymethyl methacrylate as a potential breast biopsy marker: a comparative investigation.

Since its first description 25 years ago, color Doppler twinkling has been a compelling ultrasound feature in diagnosing urinary stones. While the fundamental cause of twinkling remains elusive, the distinctive twinkling signature is diagnostically valuable in clinical practice. It can be inferred that if an entity twinkles, it empirically has certain physical features. This work investigates a manipulable polymeric material, polymethyl methacrylate (PMMA), which twinkles and has measurable surface roughness and porosity that likely contribute to twinkling. Comparative investigation of these structural properties and of the twinkling signatures of breast biopsy markers made from PMMA and selected commercially available markers showed how twinkling can improve ultrasound detection of devices intentionally designed to twinkle. While this specific application of detecting breast biopsy markers by twinkling may provide a way to approach an unmet need in the care of patients with breast cancer, this work ultimately provides a platform from which the keys to unlocking the fundamental physics of twinkling can be rigorously explored.

Lymphatic Mapping Using US Microbubbles before Lymphaticovenous Anastomosis Surgery for Lymphedema.

Background Lymphaticovenous anastomosis (LVA) surgery is an effective surgical treatment of secondary lymphedema in the extremities, but indocyanine green (ICG) fluorescent lymphography, the reference standard for imaging target lymphatic vessels, has several limitations. More effective methods are needed for preoperative planning. Purpose To evaluate whether contrast-enhanced US (CEUS) can be used to identify target lymphatic vessels for LVA surgery in patients with secondary upper extremity lymphedema and compare the results with those from ICG fluorescent lymphography. Materials and Methods In this single-center retrospective review, CEUS with intradermal injection of microbubbles was performed in patients before LVA surgery in the upper extremities between October 2019 and September 2021. All patients had secondary upper extremity lymphedema from breast cancer treatment. Technical success rate was defined as lymphatic vessels identified with use of CEUS that led to successful LVAs. Descriptive statistics were used. Results All 11 patients were women (mean age, 56 years ± 8 [SD]). The median number of microbubble injection sites was 11 (range, 8-14). CEUS helped identify lymphatic vessels in all 11 women, including in six women in whom ICG fluorescent lymphography could not be performed or failed to help identify any targets. Thirty-five explorations (median, three per patient; range, two to four) were performed, and 24 LVAs (median, three per patient; range, zero to four) were created. Of the anastomoses, 33% (eight of 24) were mapped with use of both CEUS and ICG fluorescent lymphography, 58% (14 of 24) with CEUS only, and 8% (two of 24) with ICG fluorescent lymphography only. Among the 33 explorations on targets mapped with CEUS, an anastomosis could be made at 22 sites, for a technical success rate of 67%. Seven women had at least one additional LVA created from the use of CEUS. Conclusion Contrast-enhanced US is a promising tool for identifying lymphatic vessels in the upper extremities, especially when indocyanine green fluorescent lymphography fails to depict targets or cannot be used. Published under a CC BY 4.0 license.

Safety and tolerability of liquid amikacin in antibiotic-loaded bone cement - a case series.

High-dose liquid antibiotics are uncommon in bone cement. We present a case series of patients in which up to 16 mL of liquid amikacin (250 mg mL - 1 ) was successfully incorporated into bone cement to treat periprosthetic joint infections. We did not observe adverse drug reactions definitively attributed to its use.

Bargain Hunting for Buffered Lidocaine: A Collaborative Discovery of Cost-saving Strategies That Can Improve Patient Care.

Buffered lidocaine is a local anesthetic option during percutaneous needle-directed procedures in the breast. At our institution, sodium bicarbonate (the buffer) is dispensed in volumes that frequently lead to medical waste and shortages. In this study, we describe how moving the buffering of lidocaine from the procedure room to our clinical hospital pharmacy results in a reduction in costs and improves satisfaction across the breast radiology department. While cost savings are difficult to tease out in practices that opt for bundled payments, we were able to access pricing and supply data and coordinate with our pharmacy to change our practice. Making these changes saves our practice $26 000 a year and allows us to continue to offer buffered lidocaine even during sodium bicarbonate shortages. This manuscript describes how these changes came about and their economic impact.

Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography.

Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium-based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.

Outcomes Following Three-Factor Inactive Prothrombin Complex Concentrate Versus Recombinant Activated Factor VII Administration During Cardiac Surgery.

OBJECTIVE: To compare outcomes following inactive prothrombin complex concentrate (PCC) or recombinant activated factor VII (rFVIIa) administration during cardiac surgery. DESIGN: Retrospective propensity-matched analysis. SETTING: Academic tertiary-care center. PARTICIPANTS: Patients undergoing cardiac surgery requiring cardiopulmonary bypass who received either rFVIIa or the inactive 3-factor PCC. INTERVENTIONS: Outcomes following intraoperative administration of rFVIIa (263) or factor IX complex (72) as rescue therapy to treat bleeding. MEASUREMENTS AND MAIN RESULTS: In the 24 hours after surgery, propensity-matched patients receiving PCC versus rFVIIa had significantly less chest tube outputs (median difference -464 mL, 95% confidence interval [CI] -819 mL to -110 mL), fresh frozen plasma transfusion rates (17% v 38%, p = 0.028), and platelet transfusion rates (26% v 49%, p = 0.027). There were no significant differences between propensity-matched groups in postoperative stroke, deep venous thrombosis, pulmonary embolism, myocardial infarction, or intracardiac thrombus. Postoperative dialysis was significantly less likely in patients administered PCC versus rFVIIa following propensity matching (odds ratio = 0.3, 95% CI 0.1-0.7). No significant difference in 30-day mortality in patients receiving PCC versus rFVIIa was present following propensity matching. CONCLUSIONS: Use of rFVIIa versus inactive PCCs was significantly associated with renal failure requiring dialysis and increased postoperative bleeding and transfusions.

Perioperative Use of Coagulation Factor Concentrates in Patients Undergoing Cardiac Surgery.

Coagulopathy and bleeding are common in patients undergoing cardiac surgery, with a perioperative transfusion rate in excess of 50%. The mechanism of coagulopathy associated with cardiac surgery using cardiopulmonary bypass is multifactorial. Historically, coagulation factor-mediated bleeding in such instances has been treated with allogeneic plasma transfusion. Coagulation factor concentrate use for treatment of hemophilia, congenital factor deficiencies and, more recently, emergency warfarin reversal is common. Formulations of factor concentrates include single and multifactor concentrates and both human and recombinant-derived products. Off-label use of factor concentrates for coagulopathy and bleeding associated with cardiac surgery has been described for decades; however, sound clinical research with regard to this practice is limited. This review highlights the literature discussing the use of factor concentrates in patients undergoing cardiac surgery and provides an overview of reasonable uses or lack thereof for factor concentrates in clinical practice.