Produção Nacional
Revisado por pares
The Clinical Importance of Pulsatile Flow in Extracorporeal Life Support: The Penn State Health Approach
2016; Wiley; Volume: 40; Issue: 12 Linguagem: Inglês
10.1111/aor.12875
ISSN1525-1594
AutoresAkif Ündar, Shigang Wang, Jenelle Izer, Joseph B. Clark, Allen R. Kunselman, Sunil Patel, Kaitlyn Shank, Elizabeth Profeta, Ronald P. Wilson, Petr Ošťádal,
Tópico(s)Respiratory Support and Mechanisms
ResumoRecent improvements in the safety and efficiency of components of the extracorporeal life support (ECLS) circuit have improved the mortality and morbidity of patients with severe, reversible cardiac and respiratory failure 1, 2. Circuit improvements are primarily due to optimization of the components of the circuit, namely the efficiency of the oxygenators and pumps along with better veno-arterial and veno-venous cannulae 3, 4. New ECLS systems have several advantages including significantly reduced set-up time (less than 10 min), a lower priming volume (<190 mL for pediatric and 90 mm Hg) to maintain coronary blood flow, however, the i-cor pump ECLS system applies active cardiac support in diastole when the heart is not stressed 13, while also reducing preload and increasing arterial oxygenation. By synchronizing the pulsatility of the pump to that of the patient's innate heartbeat, we avoid the formation of cannon waves from simultaneous intrinsic pulse waves and ECLS-generated pulse waves, where there is still some cardiac output from the injured heart. Additionally, because this system responds to the native heartbeat rather than to a preset one, blood flow is modulated to a degree by the patient's own autonomic nervous system, which is more physiological than an external rate. In 2014 and 2015, we evaluated the i-cor pump's ability to generate ECG-synchronized, physiological quality pulsatile flow under normal sinus rhythm and heart rate both in vitro and in vivo 13, 14. Additionally, our group documented that all extracorporeal components (pump, oxygenator, and an arterial cannula) of this particular system had significantly lower hemodynamic energy loss compared to the conventional nonpulsatile flow using the same pump console 6, 7. With this particular ECLS system, the user is able to determine the magnitude of pulsatility produced within the circuit, ranging from diminished pulsatile flow to physiological levels of pulsatility 6, 7. Pulsatility settings have a direct impact on the generation of hemodynamic energy and surplus hemodynamic energy (SHE). SHE is the extra hemodynamic energy generated from pulsatile perfusion 6, 7. Our hypothesis is that pulsatile flow maintains better organ perfusion because of this extra hemodynamic energy, or SHE levels. In contrast, under 100% nonpulsatile flow, essentially no SHE is produced 6, 7. In addition to creating higher mean arterial pressures (MAP), and surplus hemodynamic energy during pulsatile mode compared to nonpulsatile mode, we observed better end-organ protection in vivo 13. In pulsatile mode, after 24-h ECLS, the animals demonstrated higher systemic blood pressure (P: 75.6 ± 9.5 mm Hg; NP: 66.8 ± 16.1 mm Hg), required less inotropic support (P: 200 µg; NP: 1700 µg), and produced higher urine output (P: 3379 ± 443 mL; NP: 2598 ± 1012 mL). In a similar study conducted by another lab, the investigators demonstrated that the ECG-synchronized pulsatile flow created by this pump was able to restore and even significantly increase coronary artery flow during ventricular fibrillation in adult swine models 15. Dr. Ostadal and his colleagues have investigated the parameters of left ventricular (LV) function during conventional continuous flow ECLS support and ECG-synchronized pulsatile flow ECLS in cardiogenic shock 16. In their model, 10 female swine (body weight 45 kg) underwent ECLS implantation under general anesthesia and artificial ventilation. Subsequently, acute cardiogenic shock with signs of tissue hypo-perfusion was induced by global myocardial hypoxia. Hemodynamic and cardiac performance parameters were then measured at different levels of continuous or pulsatile ECLS flow (ranging from 1 L/min to 4 L/min) using arterial and venous catheters, a pulmonary artery catheter, and a LV pressure-volume loop catheter. In this particular cardiogenic shock model, myocardial hypoxia resulted in a decline in mean (±SD) cardiac output to 2.3 ± 1.2 L/min, in systolic blood pressure to 61 ± 7 mm Hg and in LV ejection fraction (EF) to 21 ± 7%. Synchronized pulsatile flow was associated with significant reduction of LV end-systolic volume (ESV), an increase in LV stroke volume, and higher EF at all ECLS flow levels in comparison with continuous ECLS flow. At selected ECLS flow levels, pulsatile flow also reduced LV end-diastolic pressure, end-diastolic volume, and SP. These results indicated that ECG-synchronized pulsatile ECLS flow preserves LV function in comparison with standard continuous-flow ECLS in cardiogenic shock. All of these in vivo results from multiple investigators suggest the important clinical implications of ECG-synchronized pulsatile flow. Although our results on ECG-synchronized pulsatile ECLS from in vitro and in vivo studies are promising, additional experiments should be performed before utilizing this novel system in patients. In particular, the duration of our experiments was limited to 24 h and, therefore, a similar study conducted for a longer duration of time (at least 1 week) is highly recommended. Additionally, the flow rate of ECLS support in our in vivo experiments was only 2.6 L/min for “partial” support, while in reality the flow rate of full support in patients may be increased up to 4 L/min. Therefore, conducting additional hemolysis experiments using this system with fresh human blood is also recommended prior to use in patients. We have already documented that surplus hemodynamic energy levels are significantly decreased in our in vitro experiments with an increased flow rate (2 L/min vs. 4 L/min) 13. In addition, we used only 18 Fr arterial cannulae for in vivo experiments. Additional in vitro and in vivo experiments are required to evaluate this novel system with varying levels of pulsatility, higher flow rates, and different sizes of arterial cannulae in both healthy and heart failure models. New generation extracorporeal life support systems include not only conventional nonpulsatile flow but also pulsatile as well as electrocardiogram-synchronized pulsatile flow, using the same console and without accruing any additional cost. An ECG-synchronized pulsatile ECLS system appeared to (i) provide superior end-organ protection with improved renal function and systemic vascular tone, (ii) significantly increase coronary artery flow during ventricular fibrillation, and (iii) better preserve left ventricular function in comparison with standard continuous-flow ECLS in cardiogenic shock. Further investigation of the perfusion modes during ECLS in vivo and in vitro is warranted. Akif Ündar, PhD Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Department of Surgery Department of Bioengineering Penn State College of Medicine, H085 500 University Drive P.O. Box 850 Hershey, PA 17033-0850, USA E-mail: [email protected] Shigang Wang, MD Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Penn State College of Medicine Jenelle M. Izer, DVM, MS Department of Comparative Medicine Penn State College of Medicine Joseph B. Clark, MD Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Department of Surgery Penn State College of Medicine Allen R. Kunselman, MA Department of Public Health and Sciences Penn State College of Medicine Sunil Patel, MBBS Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Kaitlyn Shank, BSc Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Penn State College of Medicine Elizabeth Profeta, BSc Department of Pediatrics, Penn State Health Pediatric Cardiovascular Research Center Penn State College of Medicine Ronald P. Wilson, VMD, MS Department of Comparative Medicine Penn State College of Medicine Petr Ostadal, MD, PhD, FESC Cardiovascular Center, Na Homolce Hospital, Prague, Czech Republic
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