Extracorporeal life support is a worldwide expanding technology for patients in critical cardiogenic shock. The device is usually attached to the femoral vessels using percutaneous techniques. Despite sufficient extracorporeal circulatory support, an unclear number of patients develop high end-diastolic pressures leading to left ventricular distension and pulmonary edema, and ventricular thrombus formation may evolve. This article discusses the strategies to prevent ventricular distension by conservative, interventional, and surgical means, also illustrated by case presentations.
Rationale: Sleep-disordered breathing (SDB) is frequently associated with atrial arrhythmias. Increased CaMKII (Ca/calmodulin-dependent protein kinase II) activity has been previously implicated in atrial arrhythmogenesis. Objective: We hypothesized that CaMKII-dependent dysregulation of Na current (I Na ) may contribute to atrial proarrhythmic activity in patients with SDB. Methods and Results: We prospectively enrolled 113 patients undergoing elective coronary artery bypass grafting for cross-sectional study and collected right atrial appendage biopsies. The presence of SDB (defined as apnea-hypopnea index ≥15/h) was assessed with a portable SDB monitor the night before surgery. Compared with 56 patients without SDB, patients with SDB (57) showed a significantly increased level of activated CaMKII. Patch clamp was used to measure I Na . There was a significantly enhanced late I Na , but reduced peak I Na due to enhanced steady-state inactivation in atrial myocytes of patients with SDB consistent with significantly increased CaMKII-dependent cardiac Na channel phosphorylation (Na V 1.5, at serine 571, Western blotting). These gating changes could be fully reversed by acute CaMKII inhibition (AIP [autocamtide-2 related inhibitory peptide]). As a consequence, we observed significantly more cellular afterdepolarizations and more severe premature atrial contractions in atrial trabeculae of patients with SDB, which could be blocked by either AIP or KN93 (N-[2-[[[(E)-3-(4-chlorophenyl)prop-2-enyl]-methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide). In multivariable linear regression models incorporating age, sex, body mass index, existing atrial fibrillation, existing heart failure, diabetes mellitus, and creatinine levels, apnea-hypopnea index was independently associated with increased CaMKII activity, enhanced late I Na and correlated with premature atrial contraction severity. Conclusions: In atrial myocardium of patients with SDB, increased CaMKII-dependent phosphorylation of Na V 1.5 results in dysregulation of I Na with proarrhythmic activity that was independent from preexisting comorbidities. Inhibition of CaMKII may be useful for prevention or treatment of arrhythmias in SDB. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02877745. Visual Overview: An online visual overview is available for this article.
VV ECMO in patients suffering from severe lung failure is effective in improving gas exchange with an overall survival of higher than 50%. Prolonged need of ECMO support does not have an impact on survival.
Clinical data on anticoagulation needs of modern extracorporeal membrane oxygenation (ECMO) and its impact on coagulation are scarce. Therefore, we analyzed coagulation-related parameters, need for transfusion, and management of anticoagulation in adult patients with severe acute respiratory failure during treatment with either pumpless interventional lung assist (iLA) or veno-venous ECMO (vv-ECMO). Sixty-three patients treated with iLA and 192 patients treated with vv-ECMO at Regensburg University Hospital between January 2005 and May 2011 were analyzed. Data related to anticoagulation, transfusion, and coagulation parameters were collected prospectively by the Regensburg ECMO registry. Except for a higher, sequential organ failure assessment (SOFA) score in the ECMO group (12 [9-15] vs. 11 [7-14], P = 0.007), a better oxygenation, and a lower dosage of vasopressors in the iLA patients, both groups had similar baseline characteristics. No difference was noted in terms of outcome and overall transfusion requirements. Factors of the plasmatic coagulation system were only marginally altered over time and did not differ between groups. Platelet counts in ECMO-treated patients, but not in those treated with iLA, dropped significantly during extracorporeal support. A more intense systemic anticoagulation with a mean activated partial thromboplastin time (aPTT) > 53 s led to a higher need for transfusions compared with the group with a mean aPTT < 53 s, whereas the average durability of membrane oxygenators was not affected. Need for red blood cell (RBC) transfusion was highest in patients with extrapulmonary sepsis (257 mL/day), and was significantly lower in primary pulmonary adult respiratory distress syndrome (ARDS) (102 mL/day). Overall, 110 (0-274) mL RBC was transfused in the ECMO group versus 146 (41-227) mL in the iLA group per day on support. The impact of modern iLA and ECMO systems on coagulation allows comparatively safe long-term treatment of adult patients with acute respiratory failure. A moderate systemic anticoagulation seems to be sufficient. Importantly, platelets are more affected by vv-ECMO compared with pumpless iLA.
The use of hand-held Mini-ECMO systems enables for the first time the rapid onset of extracorporeal life support independent from the patient's current location. However, success is extremely time- and team dependent. Highly skilled interdisciplinary patient management is essential to let minimised-ECMO become a new and highly effective bridge to recovery in out-of-centre cardiogenic shock patients.
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