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a Department of Cardiothoracic Surgery, University Hospital of Regensburg, Regensburg, Germany
b Department of Anesthesiology, University Hospital of Regensburg, Regensburg, Germany
Accepted for publication September 1, 2009.
* Address correspondence to Dr Schmid, Department of Cardiothoracic Surgery, University Hospital of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany (Email: christof.schmid{at}klinik.uni-regensburg.de).
| Abstract |
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Methods: We report on 18 patients initially provided with venoarterial extracorporeal membrane oxygenation and then downgraded to a pumpless arteriovenous shunt with a membrane oxygenator by removal of the pump from the circuit after hemodynamic stabilization in the face of persisting pulmonary failure. Main underlying diseases were adult respiratory distress syndrome (44%) and pneumonia (28%). Mean patient age was 44 years, and mean body mass index was 25.7 kg/m2. Anticoagulation, hemodynamic, and respiratory variables were analyzed.
Results: All patients exhibited severe cardiopulmonary failure with a mean oxygenation ratio (partial pressure of oxygen to fraction of inspired oxygen ratio) of 74 ± 43 mm Hg (mean partial pressure of oxygen, 70 ± 33 mm Hg) and a mean partial pressure of carbon dioxide of 68 ± 32 mm Hg despite maximal (ventilatory) conservative therapy (fraction of inspired oxygen, 0.98 ± 0.08). Initial serum lactate was 51 ± 43 mg/dL. The sequential organ failure assessment score averaged 11.8 ± 2.47, and the lung injury score was 3.1 ± 0.58. Total mechanical respiratory support was performed for a mean of 13.6 ± 15.7 days. After 24 hours an improvement in oxygenation and a decrease in carbon dioxide was achieved with a mean partial pressure of carbon dioxide of 40 ± 11 mm Hg (p < 0.001) and a partial pressure of oxygen of 86 ± 26 mm Hg (p = 0.031). After 6 ± 3 days of extracorporeal membrane oxygenation, patients were hemodynamically stabilized. Extracorporeal membrane oxygenation was downgraded to pumpless extracorporeal lung assist for another 10 ± 15 days (range, 2 to 71 days). Twelve patients (66.7%) could be weaned, with a 30-day mortality of 55.6%. Norepinephrine dosage could be reduced significantly within 24 hours (3.2 ± 1.8 versus 1.5 ± 1.5 mg/h; p = 0.008).
Conclusions: Respiratory support by an extracorporeal device used as last resort therapy allows rapid stabilization of patients with acute lung failure. Early replacement of extracorporeal membrane oxygenation by pumpless extracorporeal lung assist minimizes the negative side effects of extracorporeal circulation.
| Introduction |
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Since its first clinical use by Hill and O'Brien [6] and Bartlett and colleagues [7] in the 1970s, extracorporeal membrane oxygenation (ECMO) support has became a lifesaving procedure. Initially, the best outcomes were achieved in patients with postoperative cardiac failure of newborn and adults with capillary leak syndrome [6, 7]. Extracorporeal membrane oxygenation is now widely used in cases of cardiac and respiratory failure [8]. An important indication for ECMO has become severe ARDS regardless of underlying disease, for which it is considered a last resort therapy [9, 10]. Although ECMO ensures adequate oxygenation and carbon dioxide removal through pump-driven extracorporeal respiratory support, ventilation variables can be reduced to minimize ventilator-associated lung injury while supporting pulmonary recovery.
Pumpless extracorporeal lung assist therapy (PECLA, also called interventional lung assist, or iLA; NovaLung GmbH, Hechingen, Germany) uses a low-resistance membrane oxygenator interposed in an arteriovenous shunt. The system uses the blood pressure difference between arterial and venous circulations as the driving force to lead blood through an oxygenator [11, 12]. Accordingly, adequate cardiac output has to be ensured before institution of the pumpless device, and low cardiac output and hypotension are contraindications. In 1998 PECLA was first used in Regensburg for 10 days in a patient with acute pancreatitis and lung failure [11]. As oxygenation through the PECLA device is limited by blood flow and blood pressure, hypoxia still remains an indication for ECMO [12]. The advantages of the PECLA device include less artificial surface contact, with fewer side effects of pump-driven ECMO such as coagulation disorders, which are reported in 16% to 32% of those on the therapy. Also, use of a pumpless device may avoid the technical complications that occur in 2% to 6% of ECMO patients [13, 14].
The aim of the current study was to evaluate whether downgrading the extracorporeal circuit to a pumpless device and restoring physiologic pulsatile perfusion improve outcomes and reduce complications among patients with ARDS who need extracorporeal support. We report our experience with 18 patients experiencing severe circulatory failure and additional ARDS who were initially provided with pump-driven ECMO and were then switched to PECLA after hemodynamic recovery.
| Material and Methods |
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Before initiation of ECMO, a patient's hemodynamic status was assessed either by Swan-Ganz catheterization or echocardiography. Whenever possible, the diameters of the femoral vessels were measured by ultrasound, and the femoral arteries additionally scanned for arteriosclerotic changes. The cannula sizes chosen were 20% smaller than the diameter of the respective vessel. The arterial cannula (19F to 21F) was placed into the femoral or subclavian artery using the Seldinger technique, or after suturing a Dacron prosthesis (DuPont, Wilmington, DE) end-to-side to the respective vessel. The venous cannula (21F) was inserted into the femoral vein, also using the Seldinger technique. After cannula placement, the centrifugal blood pump (Rotaflow; Jostra Inc, Hirrlingen, Germany) and a membrane oxygenator (Quadrox BE, or a Quadrox PLS Bioline Coated; Maquet Inc, Hirrlingen, Germany) were connected by means of heparin-coated tubes (Fig 1). The Quadrox membrane oxygenator is made of polymethylpentene and features a flow resistance of approximately 15 mm Hg at a blood flow of 2.5 L/min. It has an inner surface of 1.3 m2. Oxygen can be applied up to 12 L/min. The priming volume of the entire system amounted to 600 mL of gelatin-based plasma expander.
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Anticoagulation
In all patients, cannulas and blood lines were coated with high-molecular-weight heparin (Bioline Coating; Maquet Inc) to avoid thrombus deposition in the system. A continuous infusion of high-molecular-weight heparin was added with the intention of maintaining a partial thromboplastin time of 60 to 70 seconds in pump-driven devices. After the centrifugal pump was removed, the target range of thromboplastin time was reduced to 50 to 60 seconds. Activated clotting time target range was 130 to 150 seconds, respectively.
Measured Variables
Fraction of inspired oxygen, arterial oxygen and carbon dioxide pressures, oxygen saturation, and serum lactate and pH were measured before establishing an extracorporeal circuit, 2 hours and 24 hours after initiation, immediately before termination, and 24 hours after termination. Flow rates in the device and respirator settings (tidal volume, peak inspiratory pressure, respirator breath rate) were noted as well. Blood samples were analyzed daily to monitor anticoagulation, hemoglobin, creatinine kinase, and hemogram levels.
Statistical Analysis
Statistical analyses were performed with Sigma-Stat 3.1 (Scientific Solutions Inc, Lausanne, Switzerland) and SPSS (SPSS Inc, Chicago, IL). Differences between survivors and nonsurvivors were calculated by Mann-Whitney-Wilcoxon test.
| Results |
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Main underlying diseases were ARDS in 44% (n = 8) of patients, caused by either previous surgery or trauma, and pneumonia in 28% of patients (n = 5). The average sequential organ failure assessment score was 11.8 ± 2.47, and the mean lung injury score was 3.1 ± 0.58. Four patients had to be resuscitated before or during venoarterial ECMO placement. In 3 patients, ECMO devices had been placed in another hospital, after which patients were transferred to our institution.
Extracorporeal Membrane Oxygenation Therapy
The femoral artery was used for arterial cannulation in 14 patients, among 6 of whom an open surgical access was necessary. The right subclavian artery was deemed favorable in 2 patients, and a Dacron prosthesis (6 mm) was sutured end-to-side to the vessel. Two patients had an intrathoracic cannulation of the ascending aorta and right atrium. In the other 16 patients, the venous cannula was inserted into a femoral vessel.
Extracorporeal membrane oxygenation caused a decline of arterial PCO 2 to 44 ± 18 mm Hg (p = 0.002) within 2 hours, whereas PO 2 was increased to 86 ± 46 mm Hg (p = 0.214). After 24 hours, a significant improvement of gas exchange was achieved in all but 1 patient; PO 2 was kept constant (86 ± 26 mm Hg; p = 0.031), and PCO 2 was decreased to 40 ± 11 mm Hg (p < 0.001). Blood pH levels normalized to 7.43 ± 0.05 (p < 0.001), and serum lactate remained at the same level (65 ± 80 mg/dL; p = 0.812). Respirator therapy could be downgraded to a lung-protective mode (FIO2 approximately 0.64 ± 0.21; p < 0.001) after the first day. The PO 2/FIO2 ratio accordingly increased significantly (156 ± 82 mm Hg; p < 0.001).
Norepinephrine dosage could be also reduced significantly (3.2 ± 1.8 versus 1.5 ± 1.5 mg/h; p = 0.008), and mean arterial blood pressure rose significantly (62 ± 20 versus 74 ± 23 mm Hg; p = 0.012) within 24 hours (Table 2).
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When extracorporeal support was stopped, the PO 2/FIO2 ratio averaged 190 ± 62 mm Hg (PO 2 approximately 87 ± 23 mm Hg, PCO 2 approximately 36 ± 11 mm Hg, FIO2 approximately 0.48 ± 0.1). Twenty-four hours later, PO 2 was 89 ± 20 mm Hg (p = 0.857) and PCO 2 was 41 ± 15 mm Hg (p = 0.686). At that time respirator therapy was performed with a mean FIO2 of 0.52 ± 0.15 (p = 0.75), and the PO 2/FIO2 ratio remained at 185 ± 65 mm Hg (p = 0.839).
Survival
Twelve patients were successfully weaned from extracorporeal support (66.7%), but 5 patients died after weaning: 2 patients underwent multiorgan failure (after 1 and 10 days, respectively), and in 1 patient ECMO had to be reestablished owing to recurrent respiratory failure on day 39 after primary successful weaning from the extracorporeal support. One patient died of circulatory collapse after 17 days, and 1 patient died as a result of general cachexia 33 days after weaning.
Six patients died during extracorporeal support: 3 patients died while on PECLA support owing to both septic shock and multiorgan-failure (2 patients) or because of acute circulatory failure (1 patient). In 3 patients, the ECMO system had to be reinstituted after initial downgrade owing to circulatory depression. All these patients in whom ECMO had to be reinstituted died during pump-driven extracorporeal support.
The entire project showed a 30-day mortality of 55.6% (10 patients), and a survival to hospital discharge of 33.3% (6 patients).
One patient who initially had been provided with an ECMO connected to the ascending aorta and the right atrium was downgraded after 9 days to a PECLA connected to the pulmonary artery and the left atrium to work as an artificial lung. After extracorporeal support for 62 days, this patient underwent double-lung transplantation [15].
A mean of 1.4 membrane oxygenators were used per patient, the most common reason for oxygenator exchange being thrombus formation (6 patients). In 3 patients thrombotic deposits were detected while receiving pump-driven support: 2 patients (1 patient with heparin-induced thrombocytopenia) showed thrombus formation both in the oxygenator and centrifugal pump. In 1 patient a system stop was caused by dislocation of the arterial cannula. During pumpless lung assistance, a clotted oxygenator had to be exchanged in 3 patients. Kinking of the tubes caused a system stop and required an exchange in 1 patient. The patient provided with a PECLA connected to the pulmonary artery and left atrium required four oxygenator exchanges during 62 days of pumpless support. In 1 patient thrombotic deposition and air leakage occurred simultaneously. Oxygenator air leakage was noted in 2 patients.
Because ischemia of the lower limb occurred in 1 patient after insertion of the arterial cannula in the femoral artery, arterial access was switched to the opposite side. As the leg ischemia spontaneously decreased thereafter, no surgical reconstruction was required. No ischemia was noted in patients with a subclavian access. Removal of the arterial cannula had to be performed surgically in 8 patients (2 subclavian, 6 femoral artery).
| Comment |
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In this patient cohort, each of whom was provided with ECMO initially and downgraded to a pumpless device afterward, the overall survival appears to be disappointing. Therefore the obvious question might be when or why to use a PECLA instead of an ECMO system. Venoarterial ECMO may seem preferable, but the systems should be tailored to the individual patient's condition. If patients with severe cardiopulmonary compromise have partially recovered and present with stable cardiac pump function and improved oxygenation, their high carbon dioxide levels must still be treated. Aggressive mechanical ventilation, such as high tidal volumes, does not appear to be sufficient for removing carbon dioxide in the presence of pulmonary inflammation, which may be caused by these factors, potentially resulting in systemic multiple organ failure. Similarly, the use of high end-expiratory pressures improves oxygenation but has no impact on carbon dioxide removal and has not been shown to reduce mortality rates from lung failure [17]. Likewise, better efficacy in oxygenation can be achieved by high-frequency oscillatory ventilation, but a beneficial effect regarding carbon dioxide removal cannot be shown [18].
Additionally, like ECMO support, invasive mechanical ventilation treatment requires sedation of the patient. In the case of hypercapnia treated solely with PECLA, sedatives can be discontinued. Even ventilation therapy might be reduced and mobilization might be performed as reported previously [15]. Patients can be weaned from the respirator, even with PECLA in place. However, when patients' gas exchange strictly depends on the extracorporeal device, technical complications may cause acute hypoxia and hypercapnia.
Bleeding complications and technical complications are common adverse side effects during extracorporeal support [13, 14]. These effects can be reduced by PECLA support. To avoid potential technical complications, removal of the blood pump appears to be beneficial. After downgrading the extracorporeal circuit, less anticoagulation is necessary. Subsequently there is a lower risk of bleeding complications, especially important among this patient population, which frequently presents an impaired coagulation system owing to multiorgan failure. Even withdrawal of heparin infusion for 2 to 3 days is made possible by an easily performed oxygenator exchange.
The most appropriate site for insertion of the arterial cannula remains a matter of discussion. Most patients in this report underwent femoral insertion of the arterial cannula with only one instance of femoral ischemia afterward; no ischemia occurred in patients who were provided with a subclavian arterial cannula. We favor subclavian access, as sufficient perfusion of the supraaortic vessels with oxygenated blood is ensured. However, before insertion an anastomosis with a Dacron prosthesis is recommended to avoid ischemia of the upper limb. The Seldinger technique may be hazardous in the subclavian site because of potential vascular laceration. The benefit of a femoral insertion site is the simple and quick accessibility, making it useful in resuscitation settings. Insertion of a cannula by the Seldinger technique is relatively easy, and low complication rates comparable to those associated with coronary angiography and percutaneous coronary interventions are reported [19, 20]. An arterial return through a femoral artery offers optimal gas exchange to the lower body, but the upper half of the body (including the coronary arteries and the supraaortic vessels) is still provided with blood that has passed through the native lungs. Thus, a high PCO 2 and a lower pH within the coronary system and the brain vessels may prevent optimal recovery of the respective end-organ function. The alternatives are to relocate the arterial return from the femoral to the subclavian artery or to implement a venovenous system. Both ECMO variations work quite well, but the inherent complications of a pump-driven device remain.
Regarding comparative costs of treatment, we leave the Quadrox BE oxygenator in the circuit (Fig 2) with higher flow resistance than the iLA Membranventilator (Novalung Inc, Hechingen, Germany), which is initially used in pumpless devices. Because oxygenator resistance depends on blood flow through the system, an estimated mean flow of 2.0 L/min yields comparable resistance both in the iLA and the Quadrox BE oxygenator.
In summary, extracorporeal support both in oxygenation and carbon dioxide removal is provided to patients in whom conventional ventilation therapy is failing. For these patients with respiratory failure and an impaired hemodynamic status, a pump-driven device has to be considered to resolve cardiovascular failure and to assure oxygenation. After hemodynamic stabilization, downgrading of the extracorporeal circuit is reasonable to restore physiologic pulsatile perfusion and to reduce the adverse effects of extracorporeal devices. Commonly it is multiorgan dysfunction or sepsis, not hypoxia or hypocapnia, that are reported as leading causes of death in these patients [21]. Therefore therapy should be focused on resolving septic shock and multiorgan failure, as cardiovascular and acute renal failure are frequent complications in nonsurviving patients [22]. Nevertheless a rather accurate selection of patients represents a substantial point for application of an extracorporeal device. Our 10-year experience reflects an overall survival rate of 35%, with best outcomes in patients after trauma compared with other disorders leading to respiratory failure [23].
In 33% of our patients, ARDS occurred after extended surgical procedures. Three patients had undergone thoracic surgery, whereas in only 1 patient aortic surgery with cardiopulmonary bypass had been performed. However, because the PECLA device is based on an arteriovenous shunt, and sufficient cardiac output as well as a mean arterial blood pressure greater than 70 mm Hg are required, we do not approve its use immediately after cardiac surgery or before stable hemodynamic status is ensured.
Despite constant efforts in improving extracorporeal devices, their use does not appear to imminently improve survival rates in ARDS [13]. At first glance, the overall mortality rate of 67% in this study may appear rather high, but the patients' impaired status with a mean sequential organ failure assessment score of 12 and a mean lung injury score of 3.1 has to be considered. Ferreira and associates [24] report mortality rates of 80% and higher with an initial sequential organ failure assessment score of more than 11 in 352 consecutive patients. A high mortality rate (exceeding 50%) was reported by Eachempati and colleagues [25] in a comparable study of ARDS patients with an initial lung injury score of 3.3. Even though no imminent benefit in survival is detectable for patients with respiratory or circulatory failure, ECMO and PECLA devices as well as life-support devices remain highly efficient tools for rescuing patients from imminent death. Therefore extracorporeal support is to be legitimately administered.
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