Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg^-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg^-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml^-1±1.2 to 27.5 ng ml^-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml^-1 ± 1.2 to 35.6 ng ml^-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.     

Extraction of bisphenol-A from a cardiopulmonary bypass circuit

We measured levels of bisphenol-A (BPA) in a priming solution and blood of a cardiopulmonary bypass (CPB) circuit. Eight circuits were used in the study of a priming solution. Blood samples were obtained from 6 patients who underwent open heart surgery after the commencement of CPB and at the termination of CPB. Another 3 samples were collected directly from the saline in a polyethylene container as a control. Then the concentrations of BPA in them were determined by means of gas chromatography. No detectable BPA was found in controls. However, a small amount was detected in the saline from the circuits (0.9 +/- 1.1 micrograms/l). A very small amount was also detected in the blood after the commencement and at the termination of CPB (0.3 +/- 0.2 microgram/l, and 0.4 +/- 0.3 microgram/l, respectively). BPA was considered to be leached from the circuit to the priming solution and the blood because the parts of the reservoir and the oxygenator were made of polycarbonate containing BPA. We suppose the BPA concentration is probably at a safe level. However, the data on the endocrinologically toxic level of blood BPA are insufficient. Therefore, the use of plastic in a circuit may require closer scrutiny to determine whether BPA contributes to exposure to xenoestrogens.     

In vivo comparison study of FDA-approved surface-modifying additives and poly-2-methoxyethylacrylate circuit surfaces coatings during cardiopulmonary bypass

The purpose of this double-blind prospective and randomized study was to examine the effects of surface-modifying additives (SMAs) and poly-2-methoxyethylacrylate (PMEA) circuits on platelet count, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood product use, extubation time, and intensive care time. Terumo noncoated, Terumo-coated (PMEA), Cobe noncoated, and Cobe coated (SMA) circuits were evaluated to find the most cost-effective way to improve patient outcomes. We aimed to find if an additional charge for a coated CPB circuit would be recovered by reducing other patient costs (blood transfusions, intensive care unit time, and bring back postoperative bleeding). An initial literature review revealed the comparison of PMEA circuits vs. noncoated circuits and SMA circuits vs. noncoated circuits in both adult and porcine models. Both SMA- and PMEA-coated circuits decreased platelet consumption, platelet factor release, and the overall perioperative inflammatory response while on cardiopulmonary bypass (CPB). The question not answered in an initial search was simply, "which coated circuit is best for the patient: SMA or PMEA?" Research comparing the above coated circuits each other was not found. The study was approved by the Institutional Review Board. Thirty patients were scheduled for elective coronary artery bypass grafting and/ or valvular repair or replacement surgery. These 30 patients were randomized as 10 patients to Terumo X-Coating (PMEA surface coating) (CT), 10 patients to Cobe Smart-X coating (SMA surface coating; CC), 5 patients to Terumo noncoated tubing (NCT), and 5 patients to Cobe noncoated tubing (NCC). Informed consent was obtained from each patient before surgery. The data showed no statistically significant relationship between platelet counts, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood products, intensive care unit time, or total hospital length of stay. Analysis revealed statistically significant clinical associations of extubation time and protamine dose with treatment group. This study provided evidence that SMA- and PMEA-coated circuits do not improve platelet consumption or decrease blood product use for patients undergoing CPB. There was statistical significance with a reduction in extubation time and total protamine requirement needed to return activated clotting time (ACT) to baseline post-CPB. Although the use of SMA and/or PMEA circuits during CPB has clinical benefit to the CPB patient, an additional charge for the specialty circuit may not be realized.     

A reusable training circuit for cardiopulmonary bypass

At the turn of the millennium, perfusion teaching programs are faced with significant difficulties. The number of students in pediatric perfusion training has increased, and more importantly, the number of pediatric open-heart procedures has decreased because of a variety of reasons. Hence, they could barely satisfy the minimum requirements of pediatric cases established by the teaching programs. The idea of "a teaching circuit" that could reproduce and simulate cardiopulmonary bypass was designed. The trainee is able to manipulate the cardiopulmonary bypass circuit according to patient responses, to perform perfusion related-maneuvers in establishing and maintaining hemodynamic stability. The aim of this study was to simulate a patient on CPB, maintain stability during varying clinical situations, and then to wean the patient off CPB. The equipment used was reusable and nonsterile.     

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.     

Rupture of extra-corporeal circuit tubing during cardiopulmonary bypass

Roller pumps are widely used for cardiopulmonary bypass in developing nations by virtue of proven safety during several years of institutional use and cost effectiveness. However, careful adjustment of roller occlusion is needed because they are known to cause spallation, tubing wear, and the occasional incident of rupture of tubing in the extracorporeal circuit. Rupture of polyvinylchloride tubing in the pump raceway during repair of a ventricular septal defect in a 4-year-old child is discussed. The event was managed by exclusion and replacement of the defective tubing during a short period of arrest. Use of an inappropriate boot pump and failure to detect its inclusion in the bypass circuit was a significant departure from protocol. However, because occlusion settings and duration of perfusion were within acceptable limits, a manufacturing flaw could also have contributed to tubing failure, and the event may or may not have been averted by the use of larger tubing. In conclusion, this incident reiterates the need for adherence to established protocol during assembly of the pump and draws attention to the fact that tubing integrity is not a guarantee and vigilance is warranted to handle its failure.     

Accuracy of temperature measurement in the cardiopulmonary bypass circuit

Oxygenator arterial outlet blood temperature is routinely measured in the cardiopulmonary bypass (CPB) circuit as a surrogate for the temperature of the arterial blood delivered to sensitive organs such as the brain. The aim of this study was to evaluate the accuracy of the temperature thermistors used in the Terumo Capiox SX25 oxygenator and to compare the temperature measured at the outlet of the oxygenator using the Capiox CX*TL Luer Thermistor with temperatures measured at distal sites. Five experimental stages were performed in vitro to achieve this aim. Under our experimental conditions, the luer thermistors accurately measured the temperature as referenced by a precision thermometer. In the CPB circuit, the difference between arterial outlet and reference thermometer temperature varied with outlet temperature over-reading at low temperatures and under reading at high temperatures. There was negligible heat loss (-0.4+/-0.1degrees C) measured at 4.5 m from the arterial outlet. The Terumo Capiox CX*TL Luer Thermistor is an accurate and reliable instrument for measuring temperature when incorporated into the Capiox Oxygenator. The accuracy in the measurement of temperature using these thermistors is affected by the thermistor immersion depth. Under reading of the arterial blood temperature by approximately 0.5 degrees C should be considered at normothermic temperatures, to avoid exceeding the maximum arterial blood temperature as described by institutional protocols. The accuracy of blood temperature measurements should be considered for all oxygenator arterial outlet temperature probes.     

A new concept of integrated cardiopulmonary bypass circuit.

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.     

In vivo evaluation of a MPC polymer coated continuous flow left ventricular assist system

The aim of this study was the evaluation of the thrombogenicity and the biocompatibility of the SunMedical EVAHEART left ventricular assist system (LVAS) coated with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer compared to a diamond-like carbon (DLC) coating. Four calves were implanted with the MPC polymer-coated LVAS. Eight calves were implanted with DLC coated LVAS. The thrombogenicity and biocompatibility of the pumps were evaluated. At explant, 60.0 +/- 37.2% (5-85%) of the pump surface area was still coated with MPC polymer after the duration of 45.0 +/- 32.0 days. In 1 out of 4 MPC and 2 out of 8 DLC coated pumps, there was a very small amount of thrombus around the seal ring; otherwise the blood contacting surfaces were free of thrombus. Major organs were normal except for a few lesions in kidneys from both groups. The MPC polymer coated EVAHEART LVAS seems to have low thrombogenicity and high biocompatibility similar to the DLC coated system. The current study demonstrated that the MPC polymer coating shows great promise for being used as an antithrombogenic substrate for the LVAS due to its ease of application, significant cost benefit, and reduction in anticoagulation therapy in acute postoperative period.     

Extraction of di-2-ethylhexyl phthalate from a cardiopulmonary bypass circuit]

We measured levels of di-2-ethylhexyl phthalate (DEHP) in a priming solution of a cardiopulmonary bypass circuit. The circuit consisted of a venous reservoir, an oxygenator, and polyvinyl chloride (PVC) tubes. Eight circuits were used in this study. In 4 circuits a heparin-coating PVC tube was used and, in the others, a non-coating PVC tube. After they were primed with 1,500 ml of saline, the saline was circulated for 30 minutes at a rate of 6 l/min at 42 degrees C. Another four samples were collected directly from the saline in a polyethylene container as a control. Then the concentrations of DEHP in them were determined by means of gas chromatography. No detectable DEHP was found in controls. But, a small amount was detected in the saline from the circuits (2.75 +/- 4.27 ppb, and 3.75 +/- 4.99 ppb, respectively). DEHP was considered to be leached from the circuit to the priming solution because the tubes were made of PVC containing DEHP as a plasticizer. We suppose the DEHP concentration is probably at a safe level. However, the data on the endocrinologically toxic level of blood DEHP are insufficient. Therefore, the use of plastic in a circuit may require closer scrutiny to determine whether DEHP leached from PVC contributes to exposure to xenoestrogens.     

In vivo uptake and elimination of isoflurane by different membrane oxygenators during cardiopulmonary bypass

BACKGROUND: Volatile anesthetics are frequently used during cardiopulmonary bypass (CPB) to maintain anesthesia. Uptake and elimination of the volatile agent are dependent on the composition of the oxygenator. This study was designed to evaluate whether the in vivo uptake and elimination of isoflurane differs between microporous membrane oxygenators containing a conventional polypropylene (PPL) membrane and oxygenators with a new poly-(4-methyl-1-pentene) (PMP) membrane measuring isoflurane concentrations in blood. METHODS: Twenty-four patients undergoing elective coronary bypass surgery with the aid of CPB were randomly allocated to one of four groups, using either one of two different PPL-membrane oxygenators for CPB or one of two different PMP-membrane oxygenators. During hypothermic CPB, 1% isoflurane in an oxygen-air mixture was added to the oxygenator gas inflow line (gas flow, 3 l/min) for 15 min. Isoflurane concentration was measured in blood and in exhaust gas at the outflow port of the oxygenator. Between-group comparisons were performed for the area under the curve (AUC) during uptake and elimination of the isoflurane blood concentrations, the maximum isoflurane blood concentration (C(max)), and the exhausted isoflurane concentration (F(E)). RESULTS: The uptake of isoflurane, expressed as AUC of isoflurane blood concentration and a function of F(E), was significantly reduced in PMP oxygenators compared to PPL oxygenators (P < 0.01). C(max) was between 8.5 and 13 times lower in the PMP-membrane oxygenator groups compared to the conventional PPL-membrane oxygenator groups (P < 0.01). CONCLUSIONS: The uptake of isoflurane into blood via PMP oxygenators during CPB is severely limited. This should be taken into consideration in cases using such devices.     

In vivo inactivation of antithrombin III is promoted by heparin during cardiopulmonary bypass.

To study the in vivo effect of heparin on antithrombin III (AT3) when elastase is elevated, the blood of 20 patients undergoing cardiopulmonary bypass (CPB) was assayed for elastase and AT3. The model was chosen because CPB is known to increase plasma elastase and the patients were heparinized. The blood of 20 patients undergoing cardiac surgery was assayed for elastase and AT3 one day preoperatively, every half hour during CPB, and one day postoperatively. Elastase increased significantly and AT3 decreased significantly during CPB. There was a direct correlation between the rise in elastase and decrease in AT3. AT3 decreased even further when elastase was elevated and patients were heparinized (AT3/elastase = 0.04 + 0.07), compared with the drop with elevated elastase alone (AT3/elastase = 0.11 + 0.14) (P less than .0015). These data indicate that (1) CPB is associated with an increase in plasma elastase, (2) elevated plasma elastase is associated with a reduction in AT3, and (3) heparin promotes the inactivation of AT3 when serum elastase is increased. These data confirm the in vitro observation that heparin accelerates the inactivation of AT3 in the presence of elastase.     

Evaluation of Mimesys phosphorylcholine (PC)-coated oxygenators during cardiopulmonary bypass in adults

A new generation of coating extracorporeal circuitry with biocompatible polymers has entered the North American perfusion market. This new biomimetic coating process uses synthetic phosphorylcholine (PC) containing polymers to bond covalently to the surface of the Sorin Monolyth oxygenator, under the brand name of Mimesys. In part one of a three-part investigation, 160 Mimesys-coated oxygenators were randomly evaluated against 36 uncoated oxygenators for blood flow, hemodynamic resistance, and pressure differentials. In part two, retrospective analysis of platelet data collected in this study was compared with platelet data collected from a previous investigation using uncoated Monolyth oxygenators with albumin and crystalloid perfusates. Part three examined the risk-adjusted clinical outcomes of 71 patients treated with Mimesys-coated oxygenators, compared with 71 case-matched patients treated with uncoated oxygenators. There was no difference found in the Mimesys-coated group, when compared to the control group, with regard to pressure differentials or hemodynamic resistance. However, we conclude that platelet protection with PC-coated Monolyth's using crystalloid perfusates, was similar to platelet protection with albumin perfusates, and significantly better than uncoated Monolyths using crystalloid perfusates.     

Development of an affordable diaphragmatic pump for cardiopulmonary bypass: an in vivo evaluation

A new diaphragmatic pump (L-Y pump) and its drive unit were developed in our institute. The pump has a priming volume of 80 ml. The pump housing is 72 mm in diameter and 42 mm in height. Its total weight is 139 g. To assess and confirm the function and controllability of this pump, comparative studies of cardiopulmonary bypass (CPB) with L-Y pump (group A) and conventional roller pump (Group B) were performed using dogs. Both pumps provided pump flow of 90 to 100 ml/kg/min. The hemodynamics of both groups were stable and within the normal range. No leakage or thrombus formation was observed in the L-Y pump. All biochemistry data showed no significant differences between the 2 groups. This data demonstrated low plasma-free hemoglobin levels in the L-Y pump group; after 120 min of CPB, mean plasma free hemoglobin levels were 48.7 +/- 8.6 mg/dl in the roller pump group and 21.4 +/- 7.1 mg/dl in the L-Y pump group, and minimal hemolysis was indicated. In conclusion, this L-Y pump and its controller system might be useful for CPB in terms of its low hemolysis and good pump quality. This pump demonstrated easy manipulation, good controllability, and provided a sufficient pulsatile flow. This pump is suitable not only for CPB, but also as a long-term circulatory support system.     

Laboratory evaluation of a low prime closed-circuit cardiopulmonary bypass system

We have explored the potential advantages of a low prime closed-circuit cardiopulmonary bypass (CPB) system using a non-human primate model. Although manufacturers have reduced priming volumes in individual CPB components, the standard circuit volume remains high because of the tubing diameter and length necessary for gravity drainage. By replacing gravity drainage with the negative pressure generated by a centrifugal pump, we can realize significant tubing volume reduction. Closed-circuit bypass was conducted on 13 baboons ranging from 5-15 kg. The circuit consisted of a centrifugal pump, a hollow fiber oxygenator, and 1/4" arterial and venous tubing. The design of the circuit included the capacity to remove a limited amount of venous air. Circulatory arrest during deep hypothermia with volume displacement into a reservoir was also accomplished with this circuit. The potential benefits of this low prime closed-circuit bypass system include blood conservation and reduction in blood surface area contact. The future safe clinical use of this type of closed-circuit bypass for routine open heart surgery will depend upon the incorporation of a device in the venous line to remove air. This is the greatest threat to patient safety in a closed circuit system and its use for open chest surgery must wait until an efficient venous air elimination device is available.