Institutional report-Cardiopulmonary bypass Aortic valve replacement with minimal extracorporeal circulation versus standard cardiopulmonary bypass

The purpose of this study was to evaluate the safety and the clinical outcomes of aortic valve replacement (AVR) performed with minimally invasive extracorporeal circulation (miniECC) technique vs. standard cardiopulmonary bypass (CPB). From February 2006 to December 2007 a total of 181 isolated AVR were performed, of these 53 patients were operated using minimal extracorporeal circulation system and 128 patients were operated using the standard CPB. Demographic characteristics and operative data were similar in both groups except for EuroSCORE (P-0.0001). Operative mortality (-30 days) was 3.8% for miniECC group and 4.7% for CPB group (Psns). Patients in both groups showed similar postoperative chest tube drainage (432"325 ml vs. 460"331 ml, Psns). The percentage of transfused patients was similar in both groups (37.7% vs. 43.8%, Ps0.45). The number of transfused blood bank products was higher in patients with a body surface area )1.7 m and who underwent traditional CPB in respect to miniECC system. Postoperatively renal injury, atrial 2 fibrillation episodes, neurologic event rate, ICU and hospital stay length were similar in both groups. The miniECC is suitable for AVR providing good clinical results but the present results should not identify the miniECC system to be superior to the conventional CPB. 2009 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.


Introduction
Cardiopulmonary bypass (CPB) induces global inflammatory reactions and induces coagulation disorders that may lead to an increased postoperative morbidity w1x.In addition, the myocardial protection during CPB is still a matter of debate.
In coronary artery bypass grafting (CABG) procedures, the off-pump technique w2, 3x is used to prevent CPB-induced inflammatory response but in open-heart surgery this is still an outstanding problem.Cardiac surgery and CPB trigger a systemic inflammatory response largely caused by the contact of blood with foreign surfaces and recirculation of activated shed mediastinal blood w3, 4x.
This inflammatory response may contribute to the development of postoperative complications, including respiratory failure, renal dysfunction, bleeding disorders, and multiple organ failure.Preventing these adverse inflammatory responses remains an important issue.
The minimally invasive extracorporeal circulation (mini-ECC) technique was successfully used in CABG to minimize the detrimental effects of extracorporeal circulation w5x.The use of miniECC provided haemodynamic stability, together with an extensive biocompatibility ensured by the reduced surface of contact and the complete coating of the CPB system, lines, and cannulae w6, 7x.
The aim of this study is to investigate the use of miniECC system in aortic valve surgery and to compare it to a standard CPB circuit with regard to postoperative clinical outcomes.

Materials and methods
Between February 2006 and December 2007 a total of 181 isolated aortic valve replacements (AVR) were performed.Of these 53 patients were operated using miniECC system and 128 patients were operated using the standard CPB.Inclusion criteria were the need of an isolated AVR.Exclusion criteria included emergency operation, redo procedure, combined procedure (double valve surgery, concomitant CABG surgery, or vascular surgery), and interatrial or interventricular septal defect.
The decision to use miniECC or standard CPB was performed individually by each surgeon on hisyher own preference.
The study conforms to the ethical guidelines of Helsinki, as reflected by the approval of the local institution's Ethics Committee.
The standard CPB circuit consists of a membrane oxygenator (Synthesis, Cobe, Soringroup, Italy), and a cardiotomy reservoir.The venous drainage was by gravity and the roller pump (Stoeckert, Soringroup, Italy) allows a non-pulsatile flow.When the body surface area was -1.8 m a pediatric 2 CPB circuit was employed (Dideco Kid, Dideco, Soringroup, Italy).
The miniECC (Synergy, Cobe, Soringroup, Italy) is a device integrating the functions of oxygenation, filtration, and air elimination in a compact manner in connection with a centrifugal pump.The venous line is directly connected to a centrifugal pump without open venous reservoir which limits the blood-air interfaces and allows reduced priming volume.At this set-up was added a vacuum bag to collect only the blood return from the vent placed in the right superior pulmonary vein and ascending aorta.This system should be considered 'semi-closed' because of the partial air-blood contact through the suction system.In our setting, air entry into the venous side is detected by an ultrasound probe and immediately stops the perfusion.The tubing set was the same for all procedures; it is composed of a custom 3y8 polyvinylchloride perfusion circuit coated with phosphorylcholine (Phisio, Soringroup, Italy).
The miniECC circuit priming volume was 900 ml, consisting of 550 ml synthetic colloid (Voluven, Fresenius Kabi, Bad Homburg, Germany) and 350 ml Ringer's lactate, whereas it was 1200 ml for CPB circuit consisting of 700 ml synthetic colloid (Voluven, Fresenius Kabi, Bad Homburg, Germany) and 500 ml Ringer's lactate, and 900 ml for the pediatric CPB consisting of 550 ml synthetic colloid (Voluven, Fresenius Kabi, Bad Homburg, Germany) and 350 ml Ringer's lactate.In our setting, air entry into the venous side is detected by an ultrasound probe and immediately stops the perfusion.
In both groups, no coated cannulae were used.In both groups, the blood from pleuro-pericardial space was exclusively collected in a cell-saving device (Electa, Dideco, Soringroup, Italy).This blood was centrifuged, washed in saline solution, recentrifugated and returned to the patient.
All patients received standard anesthetic induction using a combination of 3-5 mgykg of fentanyl, 10-20 mgykg of midazolam and 2-4% of sevoflurane.Rocuronium at a dose of 0.6-0.8mgykg was used to facilitate intubation.The use of crystalloid solution at time of induction was minimized (maximum liquid infusion accepted 300 cc of 0.9% saline solution).Intra-operative monitoring included fivelead electrocardiogram with continuous automated ST segment analysis, a radial or femoral artery catheter to measure continuous arterial pressure and a pulmonary artery catheter.The patients were selectively monitored with transesophageal echocardiography if necessary.
Anticoagulation was achieved with 5% sodium heparin (Chiesi SA, Barcelona, Spain) to maintain an activated clotting time above 480 s.
Management of CPB included systemic temperature drift to 32-34 8C, targeted mean perfusion pressure between 50 mmHg and 70 mmHg, and pump flow rates of 2.2-3.0 lyminym .Myocardial protection was achieved with an 2 intermittent, antegradeyretrograde cold blood cardioplegia solution (6 8C).
After separation from CPB, heparin was neutralized with protamine sulfate (Rovi, Barcelona, Spain) to a targeted activated clotting time within 10% of baseline.Packed red blood cells were transfused to maintain the hematocrit value above 20% during CPB and at or above 25% after CPB.
High systemic vascular resistances, which condition decreased pump flow, were treated with sodium nitroglyc-erine.Insufficient venous return was managed using fluid infusion, small doses of vasoconstrictors, the Trendelenburg position, and by checking if the venous cannula position was appropriate.
At the end of surgery patients were maintained sedated, mechanically ventilated, and transferred to the intensive care unit (ICU).Extubation and discharge from ICU were performed according to clinical criteria.

Statistical analysis
Variables are reported as mean"S.D. for continuous data, and as percentages for categorical data.Baseline characteristics and outcome were compared using the x analysis 2 for continuous categorical data and the Student unpaired t-test for continuous variables.For the categorical data, an additional Fisher's exact test was performed.The continuous parameters were also compared using the Wilcoxon-Mann-Whitney test as a non-parametric test.Differences were considered significant only with a P-0.05.Data were analyzed using the commercial package SPSS for Windows, version 12.0 (SPSS Inc, Chicago, IL, USA).

Results
Clinical characteristics are summarized in Table 1.Demographic data did not differ significantly between the two groups.The EuroSCORE and the body surface area differed significantly between the miniECC group and the CPB group.The preoperative hematocrit was also a parameter that differed between groups (miniECC 38.4"3.1 vs. CPB 37"3.4,Ps0.01).The preoperative hemoglobin was similar in the two groups.
All patients tolerated the surgical procedure in particular with regard to the CPB techniques.There were no cases of conversion from miniECC to standard CPB.Intraoperative data were also similar between groups.In the miniECC group, there were no cases of air aspiration through the venous line.In terms of postoperative complications, the miniECC group and the CPB group were also similar (Table 2) except for the discharge hemoglobin level (miniECC 9.7"0.9 vs. CPB 10.4"1.1,P-0.0001).The use of colloid and crystalloids during CPB was similar in both groups (Ps0.8).Packed red blood cells were transfused to maintain the hematocrit value above 20% during CPB and at or above 25% after CPB and in the ICU.Thirty-day mortality was similar in both groups (miniECC 3.8% vs. CPB 4.7%, Ps0.7855).

Discussion
The modern cardiac surgery has grown contemporarily with the improvement of the CPB technologies.Coronary artery surgery and heart valve surgery under CPB are considered established and safe procedures but in the last years several studies w1, 8x have outlined the importance of the so-called systemic inflammatory response (SIRS).The SIRS is not an exclusive complication of CPB but CPB remains a major factor in SIRS apparition.
The pathophysiology of SIRS is not completely known; it results in vascular injury and tissue damage by leukocyteendothelial interactions mediated by cytokines and adhe- sion molecules w2x.The complex process of SIRS involves several protein families including proinflammatory cytokines winterleukin-1 beta (IL-1b), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a)x, adhesion molecules (i.e.sVCAM-1) and chemokines (i.e.PMN elastase) w2x.Another cytokine (IL-10) might have regulatory effects during the inflammatory process w3, 4x.The assessment of the inflammatory state with CPB might be obtained by blood samples and measures in plasma of these inflammatory mediators.Several attempts were made to reduce SIRS during CPB and miniaturized closed circuits are one of these attempts because they minimize the most hazardous CPB drawbacks, e.g.hemodilution, and blood-air contact.These efforts have led to the development of the miniECC by Wiesenack and colleagues and today several models are proposed on the market w9x.
Several studies have shown that in coronary bypass surgery, the miniECC system, used as a total CPB, reduces SIRS compared to standard CPB circuit w6-11x.
This advantage in the miniECC system could be explained by the reduced priming volume and by the limits of bloodair interfaces in a closed system.However, in open-heart surgery like AVR, vent suction is needed and the advantage of the miniECC system could disappear with more bloodair interfaces in a circuit which is no more closed.
Remadi and colleagues w12x prospectively evaluated the miniECC system for AVR and showed better clinical results with preservation of renal function, decreased cardiac enzyme release, and better platelet count preservation.Their study also showed that hemodilution and blood transfusions could be potentially avoided with this perfusion approach.
Bical and colleagues w13x presented the results of their small prospective randomized trial evaluating the inflammatory response between miniECC and standard CPB circuits in aortic valve surgery.They observed an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups.There was also, in both groups, a raise after weaning from CPB, in C-reactive protein, IL-6, TNFa, neutrophil elastase, and IL-10.However, the rises of elastase, IL-10 and TNF-a were significantly lower after the weaning off miniECC compared to standard CPB.The authors concluded that in aortic valve surgery, the miniaturized CPB with the miniECC system is associated with lesser inflammation response than the standard CPB circuit.
In a recently published manuscript, Castiglioni and colleagues w14x presented their initial experience with the miniECC system in patients undergoing AVR.They prospectively compared the clinical results of 40 patients undergoing AVR and randomly assigned to receive a standard CPB or a miniECC system circuit.The authors observed that the patients in the miniECC group presented reduced chest tube drainage and blood transfusion requirements compared with patients in the CPB group (5.1% vs. 43.4%,P-0.02).Patients in the miniECC group also showed significantly higher time course of hematocrit at all time points during the operation and longer hospital stay (P-0.02)than the CPB group.Similarly, peak postoperative troponin C release was significantly lower in the study group.All the other postoperative parameters (atrial fibrillation, cerebrovascular accident, renal failure) were similar in both groups.
In the current study, we have observed that the miniECC system for AVR is a safe and reproducible method of extracorporeal circulation.We showed that the miniECC system offers a reduced priming volume, that means also a reduction of hemodilution.
Our clinical study observed a general advantage trend of the miniECC system over the CPB, only in the transfusional requirements and in the number of new cases of renal injury.Our study failed to demonstrate the superiority of the miniECC system over the conventional CPB in patients undergoing isolated AVR.The results that we have found state that there are no significant clinical differences between a miniECC semi-closed system and a traditional CPB for patients undergoing AVR.
In literature, there are only few studies published on this topic w12-15x.They all evidence a clinical or laboratory advantage in the use of the miniECC system over the CPB, despite the fact that no author gives conclusive powerful data on this topic, due to their intrinsic study limitations.
All the results presented by the different studies in literature on this topic cannot be compared between them because in all case series there were different technical aspects of the miniECC applied.In particular, the use of the vent was the most variable one.It was placed in the right superior pulmonary vein w12, 14x andyor in the pulmonary artery trunk w13-15x; in one case it was connected to the vacuum bag w12, 14x, alternatively to the cell savers w14x and in another study to a small cardiotomy w13x.The use of the cell savers also was different between studies; in one case it was used as the only suction device in the CPB group w12-15x, in another study the cell savers was used in both groups together with a roller pump suction device in the CPB group w14x.The circuit priming was also different for all the studies, it ranged from 1500 ml to 1700 ml in the CPB group and from 450 ml to 650 ml in the miniECC group w12-14x.In all studies, the use of centrifugal pump was limited only to the miniECC system group w12-14x.Femoral complete canulation was performed only in one study w15x.The concept of preoperative hemodilution during the anesthesia induction was not assessed by investigators, possibly leaving a certain degree of difference between groups of the same study and in between studies.
All these differences can act in different ways on the transfusion requirements, on the stimulation of the SIRS and finally on clinical outcomes.
Elimination of blood-air interaction is probably a major advantage of miniECC setting together with the largely reduced priming volume.In our series, we could not reach the elimination of the blood-air interaction due to the use of a left vent in the right superior pulmonary vein that converted the theoretically semi-closed system in an opensystem with pediatric priming.
After reviewing our results using the miniECC system in AVR patients we have observed that the difference in blood transfusion requirements was higher for patients with a body surface area )1.7 m 2 and who underwent traditional CPB in respect to miniECC system.The difference between the miniECC and the CPB group, in terms of blood transfusion requirements diminished significantly in case of use of pediatric CPB circuit for patients with a body surface area -1.7 m (Fig. 1).

2
This finding suggests to us that in our setting the major advantages of the miniECC system are found by using it in patients with a body surface area )1.7 m , leaving open 2 the choice for the surgeon in patients with low BSA.
Some limitations to our study should be recognized.
First, the study is a retrospective descriptive analysis of our initial experience with the miniECC system in patients undergoing AVR.Second, the sample size is certainly too small to give definitive answers.Third, some technical aspects of our strategy should be improved to obtain a 'more closed' circuit.Fourth, we have limited our analysis to clinical early outcomes.
In conclusion, our study shows that miniECC circuit can be safely used for AVR.The application of our body surface area adapted strategy shows the maximum beneficial effect of the miniECC system, in terms of reductions of blood transfusion, only for patients with a body surface area )1.7 m .Further studies, like randomized multicenter 2 studies are needed to better understand the real role of miniECC for patients undergoing AVR.