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Eur J Cardiothorac Surg 2002;21:840-846
© 2002 Elsevier Science NL

A new concept of integrated cardiopulmonary bypass circuit

Department of Cardio-vascular Surgery, Centre Hospitalier Universitaire Vaudois (CHUV), Rue du Bugnon 46, CH-1011 Lausanne, Switzerland

Received 12 September 2001; received in revised form 23 December 2001; accepted 30 January 2002.

* Corresponding author. Tel.: +41-21-314-2280; fax: +41-21-314-2278
e-mail: xavier.mueller{at}chuv.hospvd.ch

	Abstract

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Objective: Standard cardiopulmonary bypass (CPB) circuits with their large surface area and volume contribute to postoperative systemic inflammatory reaction and hemodilution. In order to minimize these problems a new approach has been developed resulting in a single disposable, compact arterio-venous loop, which has integral kinetic-assist pumping, oxygenating, air removal, and gross filtration capabilities (CardioVention Inc., Santa Clara, CA, USA). The impact of this system on gas exchange capacity, blood elements and hemolysis is compared to that of a conventional circuit in a model of prolonged perfusion. Methods: Twelve calves (mean body weight: 72.2±3.7 kg) were placed on cardiopulmonary bypass for 6 h with a flow of 5 l/min, and randomly assigned to the CardioVention system (n=6) or a standard CPB circuit (n=6). A standard battery of blood samples was taken before bypass and throughout bypass. Analysis of variance was used for comparison. Results: The hematocrit remained stable throughout the experiment in the CardioVention group, whereas it dropped in the standard group in the early phase of perfusion. When normalized for prebypass values, both profiles differed significantly (P<0.01). Both O₂ and CO₂ transfers were significantly improved in the CardioVention group (P=0.04 and P<0.001, respectively). There was a slightly higher pressure drop in the CardioVention group but no single value exceeded 112 mmHg. No hemolysis could be detected in either group with all free plasma Hb values below 15 mg/l. Thrombocyte count, when corrected by hematocrit and normalized by prebypass values, exhibited an increased drop in the standard group (P=0.03). Conclusion: The CardioVention system with its concept of limited priming volume and exposed foreign surface area, improves gas exchange probably because of the absence of detectable hemodilution, and appears to limit the decrease in the thrombocyte count which may be ascribed to the reduced surface. Despite the volume and surface constraints, no hemolysis could be detected throughout the 6 h full-flow perfusion period.

Key Words: Cardiopulmonary bypass • Hemodilution • Gas exchange

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
Whereas most research in cardiopulmonary bypass (CPB) has focused on biocompatibility, the incremental improvements in gas exchange and circuit components have resulted only in slight improvement in efficiency and size during the last three decades. CPB circuit large surface area still offers a potent stimulus for systemic inflammatory reaction [1] which may cause significant postoperative morbidity. Moreover, in standard CPB practice, hemodilution is still substantial with a significant impact on patients with low preoperative hematocrit and small body surface area [2–4].

In order to minimize these problems a new approach has been developed focusing on the overall size of the circuit (CardioVention Inc., Santa Clara, CA, USA). The resulting system is a single disposable, compact arterio-venous loop, which has integrated kinetic-assist pumping, oxygenating, air removal, and gross filtration capabilities. Placed into a drive console, the single ‘cartridge’ system is designed to be primed and ready for bypass in less than 5 min.

This study is intended to test this system ex vivo, under full-flow condition and during a prolonged period of 6 h, and to compare it with a standard circuit including a conventional hollow-fiber oxygenator. The gas exchange capacity, the effect on blood elements and the impact of hemodilution are analyzed.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
The protocol described herein were reviewed and approved by the Committee on Animal Care, Office Vétérinaire Cantonal, Lausanne. All animals received care in compliance with the Principles of Laboratory Animal Care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH Publication No. 80-23, revised 1985).

2.1. Animals
This study was conducted on 12 calves with a mean body weight of 72.2±3.7 kg (standard deviation). All the animals were premedicated with xylazine (0.15 mg/kg, given intramuscularly). General anesthesia was started with thiopentone sodium (10 mg/kg, given intravenously) and maintained thereafter with volatile anesthetic (N₂O and halothane) mixed with oxygen-enriched air. The animals were equipped with a central venous catheter and a femoral arterial catheter for hemodynamic monitoring. The animals were randomly assigned either to the CardioVention system (CardioVention group, n=6) or a standard hollow-fiber membrane oxygenator (standard group, n=6).

2.2. Integrated system
The CardioVention system is comprised of two primary components: (1) a single device which integrates the functions of oxygenation – blood pumping – and air elimination into a single unit; and (2) a low surface area closed-loop tubing circuit with built-in adaptors to accommodate more complex procedures.

The integration of three functional modules into a single unit allows the reduction of six separate connections (blood-in and blood-out connection for air-eliminator, pump, oxygenator) to two connections only. The blood flow path through the various functional modules is detailed in Fig. 1 . Blood enters the venous inlet via kinetic assistance from the centrifugal pump. The venous inlet directs blood into the air elimination module. From there, blood flows down the inlet manifold into the centrifugal pump. The centrifugal pump propels through the membrane oxygenation module and then back to the patient.

View larger version (24K): [in this window] [in a new window]   Fig. 1. The CardioVention system: longitudinal section. At the top of the integrated device, the venous blood first enters the air-elimination module (A). The centrifugal blood pump (B) module is a fixed-bearing, magnetically driven impeller pump located between the air elimination module and the oxygenating compartment (C). Black arrows, venous blood; gray arrows, oxygenated blood; white arrows, gas.

The centrifugal blood pump module is a fixed bearing, magnetically driven impeller pump. The position of the centrifugal pump enables kinetic-assisted venous drainage into the air-elimination module. The air-elimination module immediately prior to the centrifugal pump reduces the possibility of depriming the pump as can happen in conventional centrifugal pump designs used for kinetic-assisted venous drainage. As blood leaves the pump, flow is directed into the inlet manifold of the membrane module, and then through the membrane oxygenator.

The membrane oxygenator is built around a central core that passes blood from the air-elimination module to the centrifugal pump. This configuration allows all three modules to be integrated into a very small unit. The oxygenator is made up of microporous polypropylene hollow fibers (300 µm outer diameter and 50 µm wall thickness) with a total outer surface of 1.2 m². Blood flows around the outside of the fibers and gas flows inside the lumen of the hollow fibers. This setup is known for a low pressure drop between inlet and outlet of the oxygenating compartment.

Custom 3/8 polyvinylchloride (PVC) tubing packs were used for the arterio-venous loop. The total surface area of the circuit is less than 1.4 m². When each arm of the loop is cut down to 80 cm, the total priming volume of the circuit may be reduced to 400 ml. The latter configuration was used for the present experiment. The focus of development of this system has been to integrate the primary functions of the current CPB system – pumping, oxygenation, air removal – into a compact unit in order to reduce priming volume, reduce foreign surface area, and negate the use of many of the components currently being used with standard CPB technology. These components include an open hard-shell venous reservoir, a cardiotomy reservoir, an arterial line filter, and a systemic heat exchanger. Importantly, all these components may be added at the user's discretion.

The standard oxygenator used for comparison, is an integrated hollow-fiber membrane oxygenator containing an open hard shell reservoir, a heat exchanger and an oxygenating compartment. The latter contains microporous hollow fibers (380 µm outer diameter and 100 µm wall thickness) made from polypropylene for separation of the gaseous phase from the blood with a total outer surface of 2 m². The ventilating gas goes through the hollow fibers, whereas the blood circulates outside the hollow fibers mounted in a polycarbonate shell. The pump loop and the roller pump are installed between the venous reservoir (maximum volume: 5 l) on one side and the heat exchanger (laminated steel: 0.22 m²) and oxygenating compartment on the other. Therefore the blood is pushed through the space outside the hollow fibers. The cardiotomy filter is made up of a 20-µm polyester screen. Nominal flow rate is 7.5 l/min. A primary calibrated roller pump model 10.10.00, Stöckert (Sorin Biomedical, Irvine, CA, USA) and custom 1/2 and 3/8 polyvinylchloride (PVC) tubing packs were used. The total priming volume of the circuit is 1500 ml.

2.3. Cardiopulmonary bypass
Closed chest perfusion was selected for this study. For this purpose, the right atrium was cannulated through a jugular vein for venous drainage, while a carotid artery was used for the arterial return. Before cannulation, heparin (Liquemin, 300 IU/kg body weight, F. Hoffmann-La Roche, Basle, Switzerland), was given systemically. The activated clotting time (ACT, Hemochron, International Technidyne Corp., Edison, NJ) was kept above 400 s throughout perfusion. The CPB circuit was connected after being primed with crystalloid only (NaCl 104 mmol/l, KCl 5.4 mmol/l, CaCl₂ 1.6 mmol/l, MgCl₂ 1 mmol/l, Na lactate 27 mmol/l, Na bicarbonate 50 mmol/l). No additional blood was transfused. Blood flow rate was maintained at 5 l/min. Arterial pH was between 7.4 and 7.5, and mean femoral arterial pressure was maintained between 60 and 80 mmHg. Oxygen flow was supplied to the oxygenator with the gas blender at a flow rate equal to the blood flow rate and with a FIO₂ of 1. After perfusion, the animals were killed with a bolus injection of pentothal sodium.

2.4. Measurements
ECG, central venous pressure, femoral artery pressure, pump flow, inlet and outlet pressures of the oxygenator were recorded continuously. Samples for hematology (hematocrit, red blood cell, thrombocyte) and free plasma hemoglobin (Hb) were taken before bypass, after mixing (10 min bypass), and after 1, 2, 5 and 6 h of perfusion. Blood gas samples were taken before bypass and hourly during bypass. At the end of the perfusion, the oxygenator were examined for signs of clot deposits.

2.5. Data analysis
Mean and standard deviation were derived for each parameter analyzed. Student's t-test and analysis of variance for repeated measures were used where applicable for determination of statistical significance (P<0.05).

	3. Results

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
The 12 animals were perfused for 6 h according to the protocol. In both groups, mean pH varied between 7.40 and 7.50 throughout the runs. Mean arterial oxygen saturation (SaO₂) could be maintained above 99.4% in the CardioVention group and above 99.6% in the standard group. Mean venous oxygen saturation (SvO₂) could be maintained above 64% in the CardioVention group and above 61% in the standard group throughout the 6-h run in all animals.

Oxygen transfer rates during bypass are shown in Fig. 2 . Oxygen transfer rate in the CardioVention group was 191±30 ml/min after 1 h of perfusion and 209±9 ml/min after 6 h. Oxygen transfer rate in the standard group was 134±16 ml/min after 1 h of perfusion and 179±28 ml/min after 6 h. O₂ transfer rates were significantly better in the CardioVention group (P=0.04).

View larger version (9K): [in this window] [in a new window]   Fig. 2. Oxygen transfer rate. , standard oxygenator; •, CardioVention system.

View larger version (9K): [in this window] [in a new window]   Fig. 3. Carbon dioxide removal rate. , standard oxygenator; •, CardioVention system.

View larger version (9K): [in this window] [in a new window]   Fig. 4. Hematocrit (Hct). , standard oxygenator; •, CardioVention system.

View larger version (8K): [in this window] [in a new window]   Fig. 5. Red blood cell count (RBC) corrected by hematocrit and normalized by prebypass values. , standard oxygenator; •, CardioVention system.

View larger version (9K): [in this window] [in a new window]   Fig. 6. Thrombocyte count corrected by hematocrit and normalized by prebypass values. , standard oxygenator; •, CardioVention system.

View larger version (10K): [in this window] [in a new window]   Fig. 7. Free plasma hemoglobin (Hb). , standard oxygenator; •, CardioVention system.

View larger version (9K): [in this window] [in a new window]   Fig. 8. Pressure drop (P) through the oxygenator. , standard oxygenator; •, CardioVention system.

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 
In this experimental setup of prolonged full-flow perfusion, the integrated CardioVention system was compared to a classic CPB circuit including a standard hollow-fiber membrane oxygenator. With the CardioVention system, the significant hemodilution found with the classic circuit could be avoided, and both O₂ and CO₂ exchanges were improved. With its lower membrane surface area, the CardioVention system exhibited a slightly higher pressure drop, but no hemolysis could be detected in either group. The thrombocyte count profile exhibited a slighter drop in the CardioVention group than in the standard group, which may be ascribed to its lower total circuit surface.

Several problems are associated with conventional CPB, including a large number of discrete components, a large, heavy hardware console, a large priming/hemodilutional volume [5], large foreign surface area, blood damage through blood–gas admixing and shed blood reinfusion [6], microemboli generation [7] and long setup time. These characteristics contribute to patients morbidity in the following areas: hemodilution, edema, organ dysfunction, inflammatory response, blood loss and neurological complications [8–10].

The basic concept of the CardioVention system allows primarily a reduction of foreign surface area and a reduction of the priming volume. This concept results in a total surface area less than 1.4 m² which is roughly 25% of that of a standard CPB circuit, and a priming volume of 500 ml comparing favorably with the 1500 ml currently used. One of the key of this concepts is the possibility to eliminate the venous reservoir in many common procedures such as coronary artery bypass grafting. Current venous reservoirs are the single greatest contributors to foreign surface area, blood–air interface, and oil-based chemical antifoam agents exposure [11,12]. They also add to the necessary priming volume of the perfusion which increases patient hemodilution and the need for allogenic blood transfusion. Importantly though, this component may be added to the system if it becomes necessary. Another contributor to the low priming volume is the reduction of the size of the loop with 3/8 tubing used on the arterial as well as on the venous side. This concept of lower cross-section tubing has been shown to provide satisfactory drainage conditions even with a roller pump [13].

Reductions in surface area of gas exchange in order to minimize blood contact with foreign surface has been one of the mainstays of research. However, theoretically this design feature may decrease gas transfer and increase blood path resistance as well as blood trauma. On the other hand, larger surface area for gas exchange might be beneficial for patients with a high body mass index. We have previously shown the relationship between membrane surface area and gas exchange [14]. However, in the present setup, gas exchange is improved with the CardioVention System despite a smaller membrane surface area. This is most likely due to absence of detectable hemodilution effect, according to the stable Hct and red blood cell count profiles throughout the experiment, which is at variance with standard circuit. Hemodilution limits gas exchange through the reduction of gas carriers per unit of surface and volume. Limitation of hemodilution allows a higher red blood cell concentration. These results suggest that, to improve gas exchange capacity, reducing the priming volume may be more advantageous than reducing gas exchange surface area. Notably, while the improved gas exchange capacity is clear for the CO₂ (P<0.001), the difference is less striking for the O₂ (P=0.04). Nevertheless, the improved gas exchange properties of the CardioVention system is probably underestimated because this group has a somewhat lower baseline hematocrit value than the standard group. This is due to the high variability of hematocrit value in calves of this weight range [15]. Lastly, baseline hematocrit values of the calf is low, further contributing to an underestimation of the gas exchange usually seen in the clinical setting.

These advantages are achieved at the expense of a higher pressure drop through the system. However, this increase is limited, and the results are well within the acceptable range with mean values ranging between 101 and 107 mmHg, which was only slightly higher than the 76–95 mmHg range of the standard group. Importantly, the highest single value recorded in each group were similar, with 112 mmHg in the CardioVention group and 110 mmHg in the standard group. Moreover, these results did not translate into increased blood trauma, as free plasma hemoglobin was well below the clinical significant value of 100 mg/l throughout all the perfusion periods in all the animals.

Besides the reduction of the volume of the circuit with subsequent hemodilution limitation, the other target of the CardioVention system is the reduction of the foreign surface exposed to the blood in order to reduce the surface activation of blood elements and systemic inflammatory cascades. In this experiment, we focused our analysis on blood elements and the thrombocyte counts were shown to be better preserved with the CardioVention system. Damage to thrombocytes occurs as a result of interaction of the blood with the membrane surface and shear stress within the blood. CPB has been demonstrated to activate large numbers of thrombocytes which may then bind to the circuit [16], potentially causing thrombocyte number to decrease beyond what would be expected from hemodilution alone. However, circulating thrombocyte count is only a partial reflection of alterations in number of cells adherent to oxygenator membrane, and these results need to be confirmed by thrombocyte function study.

In conclusion, for this experimental setup the CardioVention system, with its concept of limited priming volume and exposed foreign surface area, improves gas exchange probably because of the absence of detectable hemodilution, and appears to limit the decrease in the thrombocyte count which may be related to the reduced surface. Despite this volume and surface constraints, no hemolysis could be detected throughout the 6 h full-flow perfusion period.

	References

Top Abstract 1. Introduction 2. Materials and methods 3. Results 4. Discussion References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Xavier M. Mueller Judith Horisberger Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mueller, X. M. Articles by von Segesser, L. K. Search for Related Content PubMed PubMed Citation Articles by Mueller, X. M. Articles by von Segesser, L. K. Related Collections Extracorporeal circulation