Comparison of Standard-Dose Versus High-Dose Dexmedetomidine in Extracorporeal Membrane Oxygenation.

BACKGROUND: Dexmedetomidine is commonly used to achieve light sedation in patients on extracorporeal membrane oxygenation (ECMO) despite minimal evidence. In vivo studies have shown dexmedetomidine sequestration in ECMO circuits, and higher doses may be used to overcome sequestration. OBJECTIVE: The purpose of this study was to compare safety and efficacy of dexmedetomidine at standard versus high doses in ECMO. METHODS: A retrospective analysis of adult ECMO patients was performed. Patients were compared as receiving either standard-dose (≤1.5 µg/kg/h) or high-dose (>1.5 µg/kg/h) dexmedetomidine. Safety outcomes included new onset bradycardia or hypotension. Efficacy was compared by the addition of concomitant sedative and analgesic agents. RESULTS: One hundred five patients were evaluated, with 20% of patients in the high-dose group. Comparing standard and high dosing, no significant differences were seen in primary safety outcomes including bradycardia (49% vs 38%, P = 0.46), hypotension (79% vs 71%, P = 0.56), or addition of vasopressors (75% vs 71%, P = 0.78). Need for concomitant analgesic agents and propofol was similar between groups. CONCLUSION AND RELEVANCE: This represents the first evaluation of use of high-dose dexmedetomidine in ECMO. Rates of dexmedetomidine higher than 1.5 µg/kg/h were commonly used in patients on ECMO, with similar rates of adverse effects and need for concomitant propofol and analgesic agents. While high-dose dexmedetomidine may be as safe as standard dose, no additional efficacy was found.

Evaluating Guideline Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction Post-coronary Artery Bypass Grafting.

Background: Limited evidence regarding the use of guideline directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG) is available. Objective: The purpose of this study was to characterize prescription of HFrEF GDMT use before and after CABG. Methods: A retrospective analysis of adult patients with an ejection fraction ≤40% undergoing CABG was performed. The primary objective was to evaluate patients receiving HFrEF GDMT, defined as a heart failure beta-blocker (HFBB) and a renin-angiotensin inhibitor preoperatively and postoperatively. Secondary outcomes included dosing, percent of patients on each individual therapy, mineralocorticoid receptor antagonist (MRA) use, and the combination thereof. The follow up period was 1 year. Results: Thirty-eight patients met criteria for inclusion. Prior to CABG, 52.6% of patients were receiving HFrEF GDMT. The prescribing rate of HFrEF GDMT was not significantly higher at any point within 1 year postoperatively (P = .299). The rate of renin-angiotensin inhibitors, HFBB, and aldosterone antagonists use significantly increased from 13.2% preoperatively to 36.8% at 1 year after CABG (P = .022). Doses of individual therapies were not significantly different across all time points preoperatively and postoperatively. Conclusion: HFrEF GDMT use and doses of individual therapies after CABG were not maximized. Collaborative efforts between cardiac surgeons, heart failure cardiologists, and pharmacists could be used to optimize HFrEF GDMT use and dose titration.

Meta-Analysis Comparing Bivalirudin Versus. Unfractionated Heparin in Adult Patients With Extracorporeal Membrane Oxygenation.

Introduction: Unfractionated heparin (UFH) has traditionally been the agent of choice in patients on extracorporeal membrane oxygenation (ECMO). However, direct thrombin inhibitors (DTI) have recently garnered more attention in ECMO because of their advantages over UFH. Given the heterogeneous results of multiple recent published studies, we performed a meta-analysis to describe pooled outcomes between bivalirudin and UFH anticoagulation in patients on ECMO. Methods: Relevant studies were identified from MEDLINE and Google Scholar database searches through April 23, 2022. The primary efficacy outcome was thromboembolism (TE), and secondary efficacy outcomes included all-cause mortality and circuit thrombosis. The primary safety outcome was major bleeding. Results: A total of 6 studies were included in the meta-analysis. Bivalirudin use was associated with significantly lower risk of TE (OR 0.61; 95% CI 0.38-.99; P = .05; I2 = 0%) and circuit thrombosis (OR 0.51; 95% CI .32-.80; P = .004; I2 = 0%) compared with UFH. There was no significant difference in all-cause mortality risk (OR 0.75; 95% CI .52-1.09; P = .13; I2 = 30%) between the bivalirudin and UFH groups. No significant difference in the risk of major bleeding between 2 groups was found (OR 0.67; 95% CI 0.25-1.81; P = .43; I2 = 80%). Conclusion: These data support that bivalirudin is a reasonable alternative to UFH in patients on ECMO. Randomized controlled trials are needed to confirm bivalirudin's efficacy and safety results compared with UFH.

Atrial Fibrillation Management: A Comprehensive Review with a Focus on Pharmacotherapy, Rate, and Rhythm Control Strategies.

Atrial fibrillation (AF) is an increasingly common arrhythmia encountered in clinical practice that leads to a substantial increase in utilization of healthcare services and a decrease in the quality of life of patients. The prevalence of AF will continue to increase as the population ages and develops cardiac comorbidities; thus, prompt and effective treatment is important to help mitigate systemic resource utilization. Treatment of AF involves two tenets: prevention of stroke and systemic embolism and symptom control with either a rate or a rhythm control strategy. Historically, due to the safe nature of medications like beta-blockers and non-dihydropyridine calcium channel blockers, used in rate control, it has been the initial strategy used for symptom control in AF. Newer data suggest that a rhythm control strategy with antiarrhythmic medications with or without catheter ablation may lead to a reduction in major adverse cardiovascular events, particularly in patients newly diagnosed with AF. Modulation of factors that promote AF or its complications is another important aspect of the overall holistic management of AF. This review provides a comprehensive focus on the management of patients with AF and an in-depth review of pharmacotherapy of AF in the rate and rhythm control strategies.

Successful treatment of intravenous drug abuser with refractory vasoplegic syndrome after mitral valve repair for infective endocarditis.

Vasoplegic syndrome, a possible complication of cardiopulmonary bypass, is a critical state of unregulated systemic vasodilation with decreased vascular resistance and a pathological insensitivity to conventional inotropes and vasoconstrictors. This case demonstrates the use of methylene blue and hydroxocobalamin as medications in the treatment of refractory vasoplegic syndrome in the context of cardiac surgery due to their differences in mechanism of action. A 24-year-old female with history of intravenous drug abuse and hepatitis C infection underwent mitral valve repair for infective endocarditis. Preoperative transesophageal echocardiography showed normal right ventricular function, left ventricular ejection fraction of 65%-75%, and severe mitral regurgitation with vegetation. In order to maintain a mean arterial pressure over 60 mmHg during cardiopulmonary bypass, norepinephrine, epinephrine, and vasopressin infusions were required. Given the patient's minimal response to these medications, a 1.5 mg/kg bolus of intravenous methylene blue was also given intraoperatively; vasoplegic syndrome remained refractory in the post-cardiopulmonary bypass period. A 5 g dose of intravenous hydroxocobalamin was administered in the intensive care unit postoperatively. Postoperative liver function tests were abnormal, and post-cardiopulmonary bypass transesophageal echocardiography revealed mildly decreased right ventricular function. While in the intensive care unit, the patient was placed on venoarterial extracorporeal membrane oxygenation and underwent therapeutic plasma exchange. Vasopressors were weaned over the course of the next 24 h. The patient was able to be transferred out of the intensive care unit on postoperative day 5. Traditional vasoconstrictors activate signal transduction pathways that lead to myosin phosphorylation. Vasodilatory molecules such as nitric oxide (NO) activate the enzyme soluble guanylyl cyclase (sGC), ultimately leading to the dephosphorylation of myosin. Nitric Oxide Synthase (NOS) can potentially increase NO levels 1000-fold when activated by inflammatory cytokines. Methylene blue is a direct inhibitor of NOS. It also binds and inhibits sGC. Hydroxocobalamin is a direct inhibitor of NO, likely inhibits NOS and may also act through additional mechanisms.

Postoperative Antibiotic Prophylaxis Following Cardiac Implantable Electronic Device Placement.

Infections related to cardiac implantable electronic device (CIED) placement are associated with poor clinical outcomes. As such, preprocedural prophylactic antibiotic therapy is indicated for all patients prior to device insertion. However, the available data are less clear on the impact of postprocedural antibiotic therapy on rates of CIED infection when used in addition to preprocedural therapy. This is single-center, retrospective cohort study of 913 patients who underwent CIED-related procedures between October 2010 and August 2014 sought to compare the rate of CIED infections in patients receiving only preprocedural antibiotics with those receiving both preprocedural and postprocedural antibiotics. Univariate analysis was used to detect independent risk factors for CIED infection. After excluding patients receiving concomitant antibiotics for other conditions, those undergoing CIED extraction alone, and those with a lack of follow-up data and/or adequate documentation of clinical encounters, 569 patients were identified for inclusion in the final analysis. The majority of patients who received postprocedural antibiotics received three to five days of therapy, with the most common antibiotic used being cephalexin. There was no statistically significant difference in the incidence of infection between patients who did and did not receive postoperative antibiotics (4.5% versus 6.1%; p = 0.398). In a multivariate analysis, the use of postprocedural antibiotic therapy was not a significant risk factor for infection (adjusted odds ratio: 0.692; 95% confidence interval: 0.314-1.525; p = 0.361). It is therefore reasonable to withhold prescribing postoperative antibiotics in patients following CIED implantation. Individualized risk factor evaluation of patient comorbidities and procedural characteristics may be needed to aid in determining whether postoperative antibiotics are reasonable in different patients. The validity of these findings is contingent on further confirmation via a prospective, randomized clinical trial.

Isavuconazole pharmacokinetics in a patient with cystic fibrosis following bilateral orthotopic lung transplantation.

Previous studies of patients with cystic fibrosis (CF) treated with azole antifungals have shown altered pharmacokinetics relative to healthy patients. Data regarding the pharmacokinetic profile of isavuconazole in patients with CF undergoing lung transplantation are currently not available. Serum trough concentrations assessed in a single CF patient following transplant revealed significantly lower values relative to available literature. Larger studies are required to validate CF population pharmacokinetics of isavuconazole.