Optimizing the Circuit of a Pulsatile Extracorporeal Life Support System in Terms of Energy Equivalent Pressure and Surplus Hemodynamic Energy

Abstract: The nonpulsatile blood flow obtained using standard cardiopulmonary bypass (CPB) circuits is still generally considered an acceptable, nonphysiologic compromise with few disadvantages. However, numerous reports have concluded that pulsatile perfusion during CPB achieves better multiorgan response postoperatively. Furthermore, pulsatile flow during CPB has been consistently recommended in pediatric and high‐risk patients. However, most (80%) of the total hemodynamic energy generated by a pulsatile pump is absorbed by the components of the extracorporeal circuit and only a small portion of the pulsatile energy is delivered to the patient. Therefore, we considered that optimizations of CPB unit and extracorporeal life support (ECLS) system circuit components were needed to deliver sufficient pulsatile flow. In addition, energy equivalent pressure, surplus hemodynamic energy, and total hemodynamic energy, calculated using pressure and flow waveforms, were used to evaluate the pulsatilities of pulsatile CPB and ECLS systems.     

Myocardial metabolism during fixed-rate pulsatile left ventricular bypass

Fixed-rate pulsatile cardiopulmonary bypass may improve subendocardial perfusion during ventricular fibrillation and has been employed during intermittent aortic cross-clamping. Variable-rate pulsatile left heart bypass that is governed by venous inflow and is asynchronous to the electrical activity of the heart is currently used in clinical practice. To study the effect of fixed-rate pulsation on myocardial metabolism during left heart bypass, six adult pigs underwent alternating periods of pulsatile (PLS) and nonpulsatile (NPLS) centrifugal pump left atrial-to-aortic bypass in randomized block design. Coronary sinus, aortic, and bypass circuit flows were recorded. Oxygen content and lactate concentration of coronary sinus and aortic blood were measured. Pulsatility index and pulse power index during pulsatile bypass were 4.4 and 4.7 (cycles/s)2, respectively. Percent bypass was maximal at a mean pulsation rate of 41.3 and averaged 92.2 and 91.3 for PLS and NPLS, respectively. Myocardial oxygen consumption per minute was reduced 14.3% during NPLS but was unchanged during PLS compared to control (CTRL). Percent lactate extraction was significantly lower than CTRL during NPLS only. Competition for inflow with the ejecting heart appeared to limit circuit pulsation rate and pulse power index. Fixed-rate pulsation is ineffective in reducing myocardial metabolism and should be avoided in left heart bypass.     

Characteristics of a Nonocclusive Pressure‐Regulated Blood Roller Pump

For decades, extracorporeal life support (ECLS) systems have relied on pumps designed for short‐term cardiopulmonary bypass. In the past, occlusive roller pumps were the standard. They are being progressively replaced by centrifugal pumps and devices developed specifically for ECLS. However, the ideal pump for long‐term bypass is yet to be created. One interesting alternative is the Rhône‐Poulenc 06 pump that is a nonocclusive pressure‐regulated blood pump developed in France in the 1970s. This pump is composed of a double‐stage rotor with three rollers at each level. The raceway tubing is stretched on the roller and pump occlusivity depends on the tension of the chamber on the rotor. The pump is able to deliver physiological blood flow values without generating dangerous negative or positive pressures. The specific design of the chamber allows the pump to generate a pulsatile flow, inducing minimal blood trauma, and to act as a bubble trap, making it inherently safe. This pump has been used for cardiopulmonary bypass, extracorporeal lung support, and more specifically single‐lumen single‐cannula venovenous membrane oxygenation for neonates, left‐heart or right‐heart assist, and venovenous bypass during liver transplant. In conclusion, this old‐fashion pump is perfectly adapted for any kind of short‐ or long‐term bypass.     

Myocardial Metabolism during Fixed-Rate Pulsatile Left Ventricular Bypass

Fixed-rate pulsatile cardiopulmonary bypass may improve subendocardial perfusion during ventricular fibrillation and has been employed during intermittent aortic cross-clamping. Variable-rate pulsatile left heart bypass that is governed by venous inflow and is asynchronous to the electrical activity of the heart is currently used in clinical practice. To study the effect of fixed-rate pulsation on myocardial metabolism during left heart bypass, six adult pigs underwent alternating periods of pulsatile (PLS) and nonpulsatile (NPLS) centrifugal pump left atrial-to-aortic bypass in randomized block design. Coronary sinus, aortic, and bypass circuit flows were recorded. Oxygen content and lactate concentration of coronary sinus and aortic blood were measured. Pulsatility index and pulse power index during pulsatile bypass were 4.4 and 4.7 (cycles/s)², respectively. Percent bypass was maximal at a mean pulsation rate of 41.3 and averaged 92.2 and 91.3 for PLS and NPLS, respectively. Myocardial oxygen consumption per minute was reduced 14.3% during NPLS but was unchanged during PLS compared to control (CTRL). Percent lactate extraction was significantly lower than CTRL during NPLS only. Competition for inflow with the ejecting heart appeared to limit circuit pulsation rate and pulse power index. Fixed-rate pulsation is ineffective in reducing myocardial metabolism and should be avoided in left heart bypass.     

A failure mode effect analysis on extracorporeal circuits for cardiopulmonary bypass

Although many refinements in perfusion methodology and devices have been made, extracorporeal circulation remains a contributor to neurological complications, bleeding coagulopathies, use of blood products, as well as systemic inflammatory response. With the exposure of these adverse effects of cardiopulmonary bypass, the necessity to re-examine the safety of extracorporeal circuits is vital. A failure mode effect analysis (FMEA) is a proven proactive technique developed to evaluate system effect or equipment failure. FMEA was used to evaluate the six different types of extracorporeal circuits based on feedback from five clinical experts. Cardiovascular device manufacturers, the Veteran's Administration National Center for Patient Safety, and the Joint Commission on Accreditation of Healthcare Organizations recommend the use of FMEA to assess and manage risks in current and developing technologies and therapies. This analysis investigates the safety of six types of extracorporeal circuits used in coronary revascularization, including the newer miniaturized extracorporeal circuits. The FMEA lists and ranks the hazards associated with the use of each cardiopulmonary bypass extracorporeal circuit type. To increase the safety of extracorporeal circuits and minimize the effects associated with cardiopulmonary bypass, perfusionists must incorporate FMEA into their clinical practice.     

Mathematical modeling of fluid dynamics in pulsatile cardiopulmonary bypass

The design criteria of an extracorporeal circuit suitable for pulsatile flow are quite different and more entangled than for steady flow. The time and costs of the design process could be reduced if mutual influences between the pulsatile pump and other extracorporeal devices were considered without experimental trial-and-error activities. With this in mind, we have developed a new lumped-parameter mathematical model of the hydraulic behavior of the arterial side of an extracorporeal circuit under pulsatile flow conditions. Generally, components feature a resistant-inertant-compliant behavior and the most relevant nonlinearities are accounted for. Parameter values were derived either by experimental tests or by analytical analysis. The pulsatile pump is modeled as a pure pulsatile flow generator. Model predictions were compared with flow rate and pressure tracings measured during hydraulic tests on two different circuits at various flow rates and pulse frequencies. The normalized root mean square error did not exceed 24% and the model accurately describes the changes that occur in the basic features of the pressure and flow wave propagating from the pulsatile pump to the arterial cannula.     

Effects of artificial circulation by pulsatile and non-pulsatile flow on brain tissues.

We examined the effects of artificial circulation by pulsatile and non-pulsatile flow on microcirculation in the brain from the viewpoints of circulation and metabolism in the brain. A centrifugal pump was fixed in the bypass in the right heart of 10 pigs. In 5 of the 10 pigs, a pulsatile flow pump was fixed in the bypass in the left heart (P group), and in the remaining 5 pigs, a centrifugal pump was fixed in the bypass in the left heart (NP group). Hemodynamics were periodically monitored for 3 hours while maintaining about 100 mmHg of the mean aortic pressure. Intracranial pressure (ICP), cerebral tissue blood flow and cerebral blood flow (CBF) were measured and compared with the initial values. As the parameters of metabolism in the brain, the cerebral oxygen consumption and lactic acid - pyruvic acid ratio were evaluated. If the cerebral blood flow was reduced by cardiogenetic shock, we suggest that blood circulation and metabolism in the brain were maintained by artificial circulation. It also indicated that there was no significant difference in blood circulation and metabolism in the brain between artificial pulsatile and non-pulsatile flow circulation.     

Evaluation of Hemolysis in a Pulsatile Assist Device for Centrifugal Pump

Abstract: To evaluate the blood trauma caused by a new device for producing a pulsatile flow of the centrifugal pump, the pulsatile assist device for the centrifugal pump (PAD-CP) that we have developed, a hemolysis study was performed in vitro and in animal experimentation. For the in vitro testing, 2 identical sets of hemolysis test circuits were prepared with 2,400 ml of bovine blood. The 2 circuits were pumped simultaneously. Plasma total hemoglobin levels were less than 40 mg/dl after 3 h, under a pump flow of 2 L/min. Hemolysis increased to a severe level after 4 h of 4 L/min pump flow. The cause of this hemolysis was thought to be a vibration of the circuit because of incomplete compression of the polyurethane tube in the PADCP. Five adult sheep (average body weight, 47 kg) were used for in vivo evaluation of hemolysis. Hemolysis was less than 30 mg/dl of plasma hemoglobin after 4 h of open chest extracorporeal circulation with 3.0–3.6 Limin of flow rate using the PAD-CP. Other hematologic changes after PAD-CP driving were within normal limits. We conclude that the PAD-CP has proven to have possible clinical applications.     

The Aachen Miniaturized Heart‐Lung Machine—First Results in a Small Animal Model

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth‐weight newborns. Taking these considerations into account, the Aachen miniaturized heart‐lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross‐clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O₂ and CO₂) may reduce circuit‐induced complications during heart surgery in neonates.     

Influence of extracorporeal circuits surface on hemostasis system during off-pump surgeries

It is demonstrated that special surface of extracorporeal circuit promotes reduction of artificial circulation negative influence on hemostasis system. During artificial circulation coating "duraflo" gradually loses its protective characteristics due to washout of heparin molecules from the surface of extracorporeal circuit, whereas chemical link between heparin and protein in "safe-line" coating is more stable. The results of the study demonstrate no advantages of heparin coating of extracorporeal circuits over protein one. Finally, all the advantages of extracorporeal circuits with "safe-line" coating lead to a decrease of postoperative blood loss.     

Clear prime for infant cardiopulmonary bypass: a miniaturized circuit

The extracorporeal circuit used clinically to perform cardiopulmonary bypass (CPB) in small infants is relatively large requiring blood to prime the circuit to reduce hemodilution. To study the merits of clear prime also in infants, we did experiments in rabbits with two extracorporeal circuits: one employing traditional venous gravity drainage (priming volume 330 ml) and the other employing vacuum drainage (priming volume 90 ml). The first circuit still had to be primed with blood, whereas the second circuit could be primed with a clear solution. Both circuits were automatically controlled to lighten the task of the perfusionist to operate the CPB safely and accurately. We demonstrated that the clear priming solution in the second circuit eliminates the hemodynamic deterioration caused by blood prime in the first circuit. Studying the effect of various modes of regulation, we showed that automatic control of CPB based on venous return is similar to autoregulation of the heart according to Starling's law, and maintains not only normal hemodynamics, but also an optimal microcirculation.     

Heparinless total left heart bypass with induced ventricular fibrillation

A new technic of extracorporeal total left heart bypass without anticoagulation is described. Left atrial and ventricular cannulas, coated with PPG, drain the blood into a bladder pump which returns blood into the descending thoracic aorta, thus establishing total left heart bypass. In acute experiments, ventricular fibrillation was electrically induced and total left heart bypass was continued for one hour (nine dogs) or four hours (one dog), after which the heart was successfully defibrillated. Near normal systemic circulation was maintained during bypass, although there was no active driving force through the pulmonary circulation except for right atrial contraction. In survival experiments ten dogs were subjected to the same procedure for one to three hours. After defibrillation they were allowed to survive for two to four weeks. Eight were long-term survivors. One died because of a technical error and the other of atelectasis. In four other dogs an autogenous saphenous vein was successfully implanted between the ascending aorta and the circumflex coronary artery using a nonthrombogenic left heart bypass with ventricular fibrillation technic. There was minimal blood loss due to elimination of anticoagulants, and the elimination of an artificial oxygenator simplified the extracorporeal circulation system. During total left heart bypass with ventricular fibrillation, inspiratory pressures were maintained at 10 mm Hg. This study indicates (1) that total left heart bypass can maintain normal systemic circulation in dogs for up to four hours during ventricular fibrillation, and (2) that this technic may be applicable to simplify coronary artery bypass surgery.     

Arterial-venous perfusion without anticoagulation: the impeller centrifugal pump

A study was designed to test the effects of the absence of anticoagulation in the extracorporeal circuit. Five swine were subjected to this experiment utilizing the impeller centrifugal pump during which neither heparin nor any other anticoagulant was used. The extracorporeal circuit consisted of polyvinylchloride tubing, a Centri-Med pump and an external stainless steel heat exchanger that was primed with albuminized Ringer's solution. An arterial-venous circuit was employed with oxygenation supplied from the subject's lungs. A series of blood aliquots were analyzed for coagulation at various times throughout the procedure. Following total body cooling using topically applied ice water, the subjects were rewarmed utilizing bypass. Within 10 minutes after the initiation of bypass, the circuits became clotted, rendering perfusion and subsequent warming ineffective. The lab values indicated that intrinsically activated coagulation occurred upon exposure to the extracorporeal apparatus. Flow visualization studies revealed a source of stagnant blood flow in the area around the hub of the pump head. Blood clot was similarly located in this area, with clot extension throughout the return circuit being realized. It is imperative that areas of stagnation be eliminated from extracorporeal circuits, since they may be potential sites for clot formation.     

Extracorporeal Circulation, Hemocompatibility, and Biomaterials

Background. Performance of a majority of cardiac surgical procedures requires the use of extracorporeal circulation. Contact of the patients' blood with the nonendothelial surface of the cardiopulmonary bypass circuit is responsible for several, potentially harmful systemic reactions.

Methods. The patients' response to extracorporeal circulation is reviewed briefly. The interactions between patient and circuit are discussed not only as they relate to blood-material contact, but also from a mechanical and rheologic standpoint. The theoretic benefits of the newer, more hemocompatible materials are presented, along with a review of published clinical experience with heparinized cardiopulmonary bypass circuits.

Results. The response to extracorporeal circulation extends far beyond a simple derangement of hemostasis. This inflammatory response is strongly influenced by the rheologic design of the circuit and by the physical and chemical properties of the surface. Heparinized circuits decrease inflammation, but the clinical benefits of this reduction remain unclear, except for extended cardiopulmonary support. The safe use of these circuits requires full heparinization and does not reduce allogeneic transfusions.

Conclusions. Clinicians are still in the search of the ideal material and the ideal extracorporeal circuit design. Newer, heparinized materials offer real but limited clinical benefits.     

Application of a pressure-relieving air compliance chamber in a single-pulsatile extracorporeal life support system: an experimental study

Nonpulsatile blood pumps are mainly used in extracorporeal life support systems. Although pulsating blood flow is known to be physiological, a pulsatile pump is not commonly applied in a circuit with a membrane oxygenator because of damage to the blood cells. The hypothesis that the placement of a pressure-relieving compliance chamber in a circuit might reduce blood cell trauma was tested. An extracorporeal life support circuit was constructed in an acute lung injury model of dogs by oleic acid infusion. The animals were divided into three groups. In group I (n = 6) a nonpulsatile centrifugal pump was used as a control. In group II (n = 4) a single-pulsatile pump was used, and in group III (n = 6) a single-pulsatile pump equipped with a compliance chamber was used. Pump flow was maintained at 1.8-2.0 L/min for 2 h. Hemodynamics and blood gas analyses indicated that the pulsatile groups II and III had better results than the nonpulsatile group I. The plasma-free hemoglobin level, which indicates blood cell trauma, was the lowest in group I and the highest in group II but was significantly decreased in group III. A pressure-relieving compliance chamber could significantly reduce high circuit pressures and blood cell trauma.     

Pulsatility Produced by the Hemodialysis Roller Pump as Measured by Doppler Ultrasound

Microbubbles have previously been detected in the hemodialysis extracorporeal circuit and can enter the blood vessel leading to potential complications. A potential source of these microbubbles is highly pulsatile flow resulting in cavitation. This study quantified the pulsatility produced by the roller pump throughout the extracorporeal circuit. A Sonosite S‐series ultrasound probe (FUJIFILM Sonosite Inc., Tokyo, Japan) was used on a single patient during normal hemodialysis treatment. The Doppler waveform showed highly pulsatile flow throughout the circuit with the greatest pulse occurring after the pump itself. The velocity pulse after the pump ranged from 57.6 ± 1.74 cm/s to ?72 ± 4.13 cm/s. Flow reversal occurred when contact between the forward roller and tubing ended. The amplitude of the pulse was reduced from 129.6 cm/s to 16.25 cm/s and 6.87 cm/s following the dialyzer and venous air trap. This resulted in almost nonpulsatile, continuous flow returning to the patient through the venous needle. These results indicate that the roller pump may be a source of microbubble formation from cavitation due to the highly pulsatile blood flow. The venous air trap was identified as the most effective mechanism in reducing the pulsatility. The inclusion of multiple rollers is also recommended to offer an effective solution in dampening the pulse produced by the pump.     

Mechanical heart support at the Deutsches Herzzentrum Berlin: Recent developments (2011)

Since the inception of the mechanical circulatory support (MCS) program at the Deutsches Herzzentrum Berlin (DHZB) in 1987, more than 1600 patients have received support with 18 different designs of technical blood pump systems, in accordance with the respective state of the art. At the beginning, pulsatile pneumatic extracorporeal ventricular assist devices (VAD) and implantable pneumatic total artificial hearts (TAH) were available, followed by pulsatile electromechanical implantable devices. At this time the assist program was based on three objectives: bridging to recovery, bridging to heart transplantation (HTx) and for permanent support. Very soon (in 1995) patients of advanced age – over 65 years – were included in the program. In 1998 rotary blood pumps with continuous flow entered the program, from 2006 edging out step by step the pulsatile systems. Today the implantable pulsatile systems have disappeared from the DHZB program, with the exception of the extracorporeal uni‐ or biventricular pneumatic EXCOR systems (Berlin Heart GmbH), which are the only systems available for newborns and children. The only approved total artificial heart is the CardioWest device, implanted in rare cases after explantation of the natural heart. Miniaturized rotary blood pumps, axial flow turbines or centrifugal radial flow pumps are leading today's market. The size and configuration of one of these pumps, the hydrodynamically and magnetically levitated HeartWare HVAD, allowed its application as a biventricular implantable assist device. The worldwide first clinical implantation of this system was performed at the DHZB in 2009. With the increasing number of patients needing immediate circulatory support and the stagnating or even decreasing number of donor hearts available for HTx, the extreme discrepancy means that other therapies are gaining increasing importance. The objectives of the MCS program therefore had to focus on permanent VADs, thus creating a growing population of long‐term outpatients with implanted systems, living with their families a near‐normal life. Within a quarter century VAD implantation has grown from an experimental procedure into an established and generally accepted therapy. Facing the rapidly increasing population of patients with end‐stage heart failure and the stagnating number of heart transplants, the use of VAD technology may represent the most advanced progress in cardiac care in the coming years. Further minaturization of the devices will allow the treatment of patients with a wide age spectrum, from newborn children to the elderly, even with biventricular support. The ultimate goal will be the development of a durable total artificial heart, based on the rotary blood pump technology, with transcutaneous energy transfer through the intact skin, guaranteeing the patients optimal quality of life for many years of support.     

Experimental Use of a Semipulsatile Rotary Blood Pump for Cardiopulmonary Bypass

Abstract: We tested our valveless pulsatile rotary blood pump (CORA) extensively in animals, but only as a temporary implantable left ventricular assist device. To expand the scope of future clinical applications, we recently undertook experiments to assess the feasibility of our pump for use in a standard cardiopulmonary bypass circuit. We conducted 4 experiments in adult sheep (body weight, 40 kg): 2 with CORA and 2 with the BioMedicus pump (BP) for comparison. In all experiments, a currently used extracorporeal circuit with reservoir, filter, and membrane oxygenator (Sorin monolith) was installed, and open chest extracorporeal circulation (ECC) was performed for 6 h. Hemodynamic performance and hemolysis were evaluated. CORA provided semipulsatile systemic flow at a level comparable to that of the BP. Free plasma hemoglobin levels were slightly higher with CORA, but the decrease in platelet count was the same for both devices. There was no significant difference in the extent of blood trauma. We conclude that CORA could be successfully used for ECC with an oxygenator. Negative pressure can be prevented by our specially designed control system.     

心内直视手术体外循环搏动灌注的临床应用

目的　观察心内直视手术体外循环搏动灌注与平流灌注的区别。　方法　将１００ 例心内直视手术患者,按灌注方法不同分为搏动灌注组与对照组,每组各 ５０ 例,分别采用搏动灌注法与平流灌注法。于转流前、转流３０ 分钟、６０ 分钟、９０ 分钟和升主动脉开放时,分别测量血浆游离血红蛋白、血小板计数,记录术中尿量,术中、术后血红蛋白尿例数,肢体末梢皮肤温度恢复时间,正性肌力药物应用时间;观察术后引流量,记录术后呼吸机应用时间和心脏自动复跳例数等,然后进行对比观察研究。　结果　搏动灌注组心脏自动复跳率提高,术中尿量增多,术后正性肌力药物应用时间减少,肢体末梢皮肤温度较对照组提前恢复２～３ 小时,提前拔气管插管６～１０ 小时,转流中血小板两组无差异;血浆游离血红蛋白随搏动时间延长逐步增高,术中、术后血红蛋白尿例数有所增加,但两组无差异;术后渗血引流量两组无差异。　结论　搏动灌注方法较符合生理状况,明显优于平流灌注方法。     

Development of the MEDOS/HIA DeltaStream extracorporeal rotary blood pump

The DeltaStream blood pump has been developed for extracorporeal circulation with one focus on potential integration into simplified bypass systems (SBS). Its small size and an embedded electric motor are the basic pump properties. A variation of the impeller design has been performed to optimize hydraulic and hematologic characteristics. A simple impeller design was developed which allows flow and pressure generation for cardiopulmonary bypass applications. The option of a pulsatile flow mode for ventricular assist device applications also was demonstrated in vitro. Impeller washout holes were implemented to improve nonthrombogenicity. The pump was investigated for potential thermal hazards for blood caused by the integrated electric motor. It could be demonstrated that there is no thermal risk associated with this design. Durability tests were performed to assess the lifetime of the pump especially with regard to the incorporated polymeric seal. Seal lifetimes of up to 28 days were achieved using different blood substitutes. In animal tests using either the pump as a single device or in an SBS setup, biocompatibility, low hemolysis, and nonthrombogenicity were demonstrated. In summary, the DeltaStream pump shows great potential for different extracorporeal perfusion applications. Besides heart-lung machine and SBS applications, ventricular assist and extracorporeal membrane oxygenation up to several days also appear promising as potential applications.