Needs assessment findings have been key tools to spark action and guide the implementation of national programs to eliminate obstetric fistulas throughout Africa and Asia.
OBJECTIVES: Extracorporeal membrane oxygenation is a potentially life-saving intervention in refractory cardiopulmonary failure, but it requires anticoagulation to prevent circuit thromboses, which exposes the patient to hemorrhagic complications. Heparin has traditionally been the anticoagulant of choice, but the direct thrombin inhibitor bivalirudin is routinely used in cases of heparin-induced thrombocytopenia and has been suggested as a superior choice. We sought to examine the timing of hemorrhagic and thrombotic complications after extracorporeal membrane oxygenation cannulation and to compare the rates of such complications between patients anticoagulated with heparin versus bivalirudin. DESIGN: Retrospective cohort study. SETTING: Johns Hopkins Hospital patients between January 2016 and July 2019. PATIENTS: Adult (> 18 yr) extracorporeal membrane oxygenation patients. INTERVENTIONS: Patients were anticoagulated either with heparin or bivalirudin. MEASUREMENTS AND MAIN RESULTS: We compared rates of hemorrhagic and thrombotic complications by time on heparin versus bivalirudin and characterized the average time to each complication. Of 144 extracorporeal membrane oxygenation patients (mean age 55.3 yr; 58% male), 41% were on central venoarterial extracorporeal membrane oxygenation, 40% on peripheral venoarterial extracorporeal membrane oxygenation, and 19% on venovenous extracorporeal membrane oxygenation. Thirteen patients (9%) received bivalirudin during their extracorporeal membrane oxygenation run, due to concern for (n = 8) or diagnosis of (n = 4) heparin-induced thrombocytopenia or for heparin resistance (n = 1). The rate of hemorrhagic or thrombotic complications did not differ between heparin (0.13/d) and bivalirudin (0.06/d; p = 0.633), but patients on bivalirudin received significantly fewer blood transfusions (1.0 U of RBCs/d vs 2.9/d on heparin; p < 0.001). CONCLUSIONS: Our results confirm the safety and efficacy of bivalirudin as an alternative anticoagulant in extracorporeal membrane oxygenation and suggest a potential benefit in less blood product transfusion, although prospective studies are needed to evaluate the true effect of bivalirudin versus the disease processes that prompted its use in our study population.
Background: Myocytes exposed to stress exhibit significant swelling and reduced contractility. These consequences are ameliorated by adenosine triphosphatesensitive potassium (K ATP ) channel opener diazoxide (DZX) via an unknown mechanism. K ATP channel openers also provide cardioprotection in multiple animal models. Nitric oxide donors are similarly cardioprotective, and their combination with K ATP activation may provide synergistic benefit. We hypothesized that mitochondria-targeted S-nitrosating agent (MitoSNO) would provide synergistic cardioprotection with DZX. PERSPECTIVE Diazoxide (DZX) with hyperkalemic cardioplegia is cardioprotective via an unknown molecular mechanism of action; however, DZX combined with cardioprotective mitochondrial S-nitrosating agent is detrimental. These results clarify the mechanisms and conditions necessary for DZX cardioprotection. Elucidation of DZX's mechanism of action will allow for its safe use in clinical trials in humans.See Commentaries on pages 355 and 357.
Background ATP‐sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase‐3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; P =0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; P =0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; P <0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure ( P <0.01) and maximum change in ventricular pressure during isovolumetric contraction ( P <0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.
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