Minimal extracorporeal circulation (MECC) is a recently introduced closed system that does not utilize cardiotomy suction or an open venous reservoir and seems to attenuate neutrophil activation and cytokine release after coronary artery bypass grafting (CABG).1–4 This technique is now widely performed in CABG,5,6 and the use of MECC for aortic valve replacement (AVR) was reported to be feasible with satisfactory outcomes.7–9 We have developed our own minimal cardiopulmonary bypass (mini-CPB) system, and we have used it for AVR since 2005. Herein, we evaluated the potential clinical advantages of mini-CPB for AVR.
Materials and Methods
We prospectively studied 32 patients who underwent isolated AVR using either mini-CPB (group M, n = 13) or conventional CPB (group C, n = 19) between 2005 and 2007. Patients who underwent concomitant surgery or repeated surgery, emergency cases, and patients on hemodialysis were excluded from this study. All patients signed an informed consent form before study entry, and the study was approved by the ethics committee of University Hospital of Hyogo College of Medicine. The first four patients were assigned to group C. Thereafter, a blind randomization was used in which each patient was assigned to either group M or C by drawing two letters. The main preoperative data for both groups were similar (Table 1). All patients underwent preoperative transesophageal echocardiography to confirm the absence of interatrial septal defects (patent fossa ovalis).
The closed mini-CPB system used in group M comprised a pump (Capiox SP45X; Terumo, Tokyo, Japan) and oxygenator (Capiox RX25; Terumo) with a 1,600-ml closed, flexible venous sheet reservoir (Capiox Flexible Venous Reservoir, Terumo), which eliminated the blood-air interface and allowed us to reduce the priming volume from 1,600 ml to 750–900 ml. The circuit was primed with 400–550 ml of Ringer's lactate solution, 150 ml of 20% mannitol, and 200 ml of 20% albumin. The entire circuit was completely covered with a poly-2-methoxyethyl acrylate (PMEA) coating to minimize the adsorption and denaturation of proteins and blood cells during extracorporeal circulation10,11 (Figure 1). The closed system does not have a cardiotomy reservoir, and intrapericardial blood was drained using a cell salvage device (Cell Saver 5; HAEMONETICS®, Braintree, MA). The circuit system for group C comprised the same membrane oxygenator and centrifugal pump. By contrast, the venous reservoir was open, and the intrapericardial blood was returned to this reservoir via a suction line. The circuit was covered with the same PMEA coating.
The surgery in both groups was performed via a full median sternotomy with moderate hypothermia (mean bladder temperature, 32°C). A full heparin dose (300 IU/kg) was administered intravenously, and the activated clotting time was maintained for >400 seconds in both groups (Hemochron; International Technidyne Inc., Edison, NJ). After aortic cross-clamping, myocardial protection was achieved by antegrade cold blood cardioplegia every 20–30 minutes. In cases of aortic insufficiency, retrograde cold blood cardioplegia and selective antegrade cardioplegia were used. Retrograde cardioplegia was not used in group M because blood cardioplegia returned to the coronary ostia and was drained by a cell salvage device. A single, two-stage right atrial cannula was used for venous drainage in both groups.
In group M, double venous purse-string sutures were placed to prevent air entry and to keep the system completely airtight. In addition, if air did enter, air embolisms were avoided using an arterial air filter. A vent was placed in the pulmonary artery, and a dry surgical field was maintained by venting, which was drained by gravity. This venting was controlled to fill the left ventricle with blood and to prevent air from entering left atrium. After declamping the aorta, an aortic root vent was connected to the flexible venous sheet reservoir to evacuate the residual intracardiac air. In group C, a vent tube was placed in the left ventricle via the right upper pulmonary vein and connected to the open venous reservoir.
Biochemical and Hematological Measurements
Blood samples (2 ml) were collected for biochemical studies into tubes containing ethylenediamine tetraacetic acid to determine interleukin (IL)-6 and IL-8 levels before and at 6 and 12 hours after CPB. The samples were immediately centrifuged at 3000 g and stored at −80°C.
The cell-salvaged blood volume and blood transfusion volume during CPB were evaluated. The hemodilution ratio was calculated as the priming volume divided by the circulating volume plus the priming volume.
All continuous data are expressed as means ± SD. The clinical characteristics of the two groups were compared with analysis of variance for continuous data and t tests or Fisher's exact test for categoric data. Nonnormally distributed data were analyzed with the Mann-Whitney rank sum test. All statistical analyses were performed using StatMate III software (ATMS Co., Ltd., Tokyo, Japan). Differences were considered significant at p < 0.05.
No major postoperative complications (bleeding, convulsion, infection, and heart failure) occurred, and none of the patients died during hospitalization in either group. Arrhythmia (atrial fibrillation or atrial flutter) was the most frequent postoperative complication in both groups (group M versus group C: 46% vs. 37%, p = 0.61).
The hemodilution ratio just after starting CPB was significantly lower in group M than in group C (14% ± 2% vs. 25% ± 3%, p = 0.0009; Figure 2).
As shown in Table 2, the levels of IL-6 increased significantly after surgery in both groups (group M: p = 0.0009; group C: p = 0.00045), but the postoperative levels at 6 and 12 hours after CPB were significantly lower in group M than in group C. The levels of IL-8 increased significantly after surgery in both groups (group M: p = 0.008; group C: p = 0.044), but there was no difference between the two groups at either time.
The volume of salvaged blood was significantly higher in group M than in group C (1337 ± 951 ml vs. 379 ± 168 ml, p < 0.001), and the amount of retransfused salvaged blood was significantly higher in group M than in group C (304 ± 369 ml vs. 104 ± 318 ml, p < 0.001). However, the volumes of infused fluid, red cell concentrate, and fresh frozen plasma during the operation did not differ between the two groups (Table 3).
The use of MECC for AVR was first reported in 2004.7–9 The main advantages of MECC for AVR were reported to include significantly reduced chest tube drainage and blood transfusion requirements8,9; significantly higher hematocrit8,9; significantly higher platelet count at intensive care unit admission7–9; better preservation of renal function7; and significantly lower neurologic event rate,7 postoperative troponin I level,7,9 and peak serum cardiac troponin T8 level.
In our study, the hemodilution ratio and serum IL-6 levels were significantly lower in the mini-CPB group. Our finding of lower hemodilution ratio is compatible with the reported higher hematocrit with this procedure.8,9 However, the clinical advantages of mini-CPB in terms of blood transfusion or fluid infusion are unclear, as demonstrated by Remadi et al.7 who found no significant differences between the CPB and MECC groups in terms of hemoglobin and hematocrit evolution after the first 48 hours. Our finding of lower serum IL-6 levels suggests beneficial effects of mini-CPB on cardiac function, respiratory function, and blood loss.
For example, in some patients, we used a cell salvage device to maintain a dry operative field, which required the management of large volumes of shed blood in these patients. Separated shed blood can be processed in the cell salvage device to retrieve red blood cells and remove potentially detrimental humoral factors.12–14 On the other hand, significantly increased concentrations of proinflammatory cytokines have been reported in cell-salvaged blood.15 In this study, the postoperative levels of IL-6 were significantly lower in group M. Therefore, we believe that the attenuation of inflammatory markers in group M was due to the processing of shed blood by the Cell Saver, which normalized the levels of IL-6 and IL-8.16–18
It was reported that the application of the MECC system requires the surgical and anesthetic teams to undergo a considerable learning curve, and it is not as safe as standard CPB because of the absence of an open venous reservoir.7 Indeed, in our experience, a high level of skill must be developed before applying the mini-CPB for AVR. Applying mini-CPB for AVR is considered to be more difficult than conventional CPB because of the potential for air embolisms and bleeding complications, even though the procedure initially seems to be quite simple. Air intake on the venous side increases the risk for embolism; therefore, we place two purse-string sutures on the right atrium and use an air filter in the arterial line. The use of an air filter on both the arterial and venous sides should reduce the risk for air embolism. However, the benefit of a low hemodilution ratio in mini-CPB is diminished if two air filters are used. We believe that one air filter in the arterial line is sufficient to prevent air embolism.
AVR can be performed with mini-CPB, which offers an alternative to conventional CPB and has some advantages in terms of hemodilution and serum IL-6 levels. However, the clinical advantages of mini-CPB are not clear and it is unlikely to become the standard procedure for AVR.
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