First experience with closed circuit/centrifugal pump extracorporeal circulation: cellular trauma, coagulatory, and inflammatory response
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《血管的通路杂志》
Department of Cardiothoracic Surgery, Heart-Center Brandenburg, Bernau, Germany
Abstract
Closed circuit extracorporeal circulation comprising a centrifugal pump has been developed to reduce deleterious effects of standard cardiopulmonary bypass. This study compares such a system with standard extracorporeal circulation (ECC). Twenty patients underwent isolated routine coronary artery revascularization. Ten patients underwent ECC. Ten patients were operated upon using a closed circuit/centrifugal pump system with coated surfaces (ISS) (SYNERGY, Stckert). Both groups did not differ regarding age, body mass, left ventricular function, number of bypasses, and concomitant diseases. Free hemoglobin (fHb), plasmin–antiplasmin complex (PAPc), platelet function (ROTEG), and interleukin 6 (IL-6) were measured preoperatively, intraoperatively (after sternotomy, during X-Clamp, during reperfusion, post ECC or ISS), and postoperatively. Technical problems were not observed. The ISS group demonstrated significantly less fHb during bypass, a lower intraoperative myocardial damage as well as less increase in IL-6 after bypass and postoperatively compared to ECC. In ISS fluid balance was significantly lower than in ECC whereas drainage loss and hospitalization did not differ statistically. Extracorporeal circulation with a closed circuit/centrifugal pump system can be routinely employed and appears to be safe. Intraoperative and early postoperative reduction of red blood cell trauma and inflammation are of potential value.
Key Words: Minimally invasive cardiopulmonary bypass
1. Introduction
ECC is still reported to evoke inflammatory reactions [1]. Blood exposure to artificial surfaces activates complement, leukocytes, and coagulation cascades [2]. Closed extracorporeal circulation has recently been developed to reduce deleterious effects of ECC [3]. This study compares the effects of a closed system with ECC on red blood cell damage, coagulation activation, fibrinolysis and cytokine expression to evaluate safety, efficacy, and clinical benefits of such a system.
2. Methods
Twenty patients underwent elective coronary revascularization for triple-vessel disease. All patients showed a low risk profile. Two groups (n=10) were defined: Standard ECC and ISS. The patients were randomly allocated to either system by means of envelopes opened by the perfusionist directly before the procedure. In all patients the LITA and a respective number of vein grafts were used.
The ISS is a device which integrates the functions of oxygenation, filtration, and air elimination in a compact manner in connection with a centrifugal pump.
When the air-eliminator sensor detects air a signal travels from the sensor to a control box so that the perfusionist can open an outlet. The tubing set is composed of custom 3/8 polyvinylchloride perfusion circuit coated with Phosphorylcholine (Phisio, Sorin). The total surface area of the circuit is <1.4 m2. The focus of development of this system has been to integrate primary functions of current ECC systems into a compact unit in order to reduce priming volume and foreign surface area.
In ISS patients arterial canulation was performed via the ascending aorta. A single tailored two-stage right atrial cannula (Stckert) was used for venous drainage. Air free venous connection was required. The initial priming volume in our setting was 950 ml, containing 850 ml electrolyte- solution, 1 million IU aprotinin and 5000 I.E. heparin versus 1850 ml in our standard ECC. Antegrade low-volume warm- blood cardioplegia (Calafiore) was administered in all patients. A cell saver system was used.
In each group blood samples were taken at the following 6 time points: preoperatively (I), intraoperatively (after sternotomy (II), 20 min postclamping (III), 10 min postdeclamping (IV), prior sternal closure (V), and 24 h postoperatively (VI). The following laboratory assessments were performed:
FHb as an important parameter to evaluate hemolytic anemia, especially intravascular hemolysis; Thrombin–antithrombin complex (TATc) as a marker of coagulation activation; Rotational thromboelastography (ROTEG Instrumantation, Germany) provides the viscoelastic measurement of clot strength in whole blood; Interleukin 6 (IL-6) as a potent mediator of the inflammatory; all Standard parameters.
Statistical analysis was performed using SPSS statistical package for Windows.
3. Results
Demographic data did not differ significantly between the groups (Table 1). Eighteen patients were male. As illustrated in Table 1, there were significant differences between ISS and ECC group with regard to duration of pump time and aortic cross-clamp time. In-hospital stay was lower for ISS patients, but without significance. All patients exhibited an uneventful course without significant complications. The detected Creatincinase- Mb-levels indicated a lower intraoperative myocardial damage in the ISS group than in the ECC group. The differences, however, disappeared after 24 h postoperatively [4].
The time course of IL-6 release in peripheral blood showed alterations. In the ECC group the noted increase was more rapid and the levels remained more elevated. However, only at time point V a significant difference was noted (P=0.003) ISS 17.3±11 pg/ml, ECC 46.4±23 pg/ml.
FHb showed a sharp increase during operation in ECC with a peak value more than fivefold higher than the only moderately elevated, corresponding levels of ISS patients. On POD 1 levels gradually dropped in both the ISS and the ECC group (Fig. 1).
There was a moderate intraoperative decrease of AT III levels noted in the ISS and the ECC group during the operation.
In both groups total platelets count did not react significantly. Data of the ROTEG did not reveal significant differences.
The surgeon's view towards the coronary vessels was not impeded by the absence of an active coronary vent. All operations with the ISS system were performed without detecting relevant air incorporation. Careful handling resulted in an amount of 250–380 ml blood concentrate for retransfusion after cell saver use.
4. Discussion
Different strategies to reduce inflammation during CABG have already been investigated: OPCAB; Coated systems comprising various inert substances [5,6]; pump optimization with centrifugal pumps [7].
The recently developed ISS is based on a concept of a short, closed circuit with coated surfaces. The present study demonstrated satisfactory clinical applicability of the new technique. Our results indicate that the use of the ISS system indeed resulted in a markedly reduced blood cell damage as well as a reduced alteration of the coagulation-cascade when compared with patients operated on ECC. These differences in activation of the coagulation pathway are remarkable because it has been demonstrated previously by Ovrum et al. [8] that a profound activation of coagulation through the interaction of blood with nonendothelial surfaces of the bypass circuit appeared to be inevitable.
IL-6 is a key mediator in the acute-phase response in infection. Elevation of plasma IL-6 level occurs both after cardiac operations with ECC [9] and after major noncardiac operations [10]. In our study a marked IL-6 response in the ECC group on the first postoperative day was noted to being higher than the values of the ISS group. This implies the induction of an intensified acute-phase response and suggests a greater degree of tissue trauma when using ECC.
In this pilot trial only patients with low comorbidities were involved. Therefore, clinical consequences of the alterations observed did perhaps not occur due to the maintained physiological compliance of these patients. We have encountered significant differences in the duration of cardiopulmonary bypass. Hence it is possible that the surgeon using ISS performed the procedure in a more alert and straightforward manner. Finally, the investigated cohorts were too small to obtain a reasonable clinical perspective.
Nevertheless, CABG with a closed system can be routinely employed and appears to be safe. Perioperative reduction of red blood cell trauma, coagulation disturbances and inflammation are of potential value.
References
Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983; 86:845–857.
Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. New Eng J Med Feb 26, 1981; 304:497–503.
Abdel-Rahman U, zaslan F, Risteski PS, Martens S, Wimmer Greinecker G. Initial experience with a minimized extracorporeal bypass system: Is there a clinical benefit Ann Thorac Surg 2005; 80:238–244.
Immer FF, Pirovino C, Gygax E, Englberger L, Tevaearai H, Carrel TP. Minimal versus conventional cardiopulmonary bypass: assessment of intraoperative myocardial damage in coronary bypass surgery. Eur J Cardiothorac Surg 2005; 28:701–704.
Fromes Y, Gaillard D, Ponzio O, Chauffert M, Gerhardt MF, Deleuze P, Bical OM. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation. Eur J Cardiothorac Surg Oct 2002; 22:527–533.
Albes JM, Sthr IM, Kaluza M, Siegemund A, Schmidt D, Vollandt R, Wahlers T. Physiological coagulation can be maintained in extracorporeal circulation by means of shed blood separation and coating. J Thorac Cardiovasc Surg 2003; 126:1504–1512.
Parolari A, Alamanni F, Naliato M, Spirito R, Franzè V, Pompilio G, Agrifoglio M, Biglioli P. Adult cardiac surgery outcomes: role of the pump type. Eur J Cardiothorac Surg 2000; 18:575–582.
Ovrum E, Brosstad F, Am Holen E, Tangen G, Abdelnoor M. Effects on coagulation and fibrinolysis with reduced versus full systemic heparinization and heparin-coated cardiopulmonary bypass. Circulation Nov 1, 1995; 92:2579–2584.
Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg Apr 2000; 69:1198–1204.
Nijsten MW, DeGroot ER, Tenduis HJ. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Colch) 1990; 79:1611–1615.(Sren S. Just, Torsten Mül)
Abstract
Closed circuit extracorporeal circulation comprising a centrifugal pump has been developed to reduce deleterious effects of standard cardiopulmonary bypass. This study compares such a system with standard extracorporeal circulation (ECC). Twenty patients underwent isolated routine coronary artery revascularization. Ten patients underwent ECC. Ten patients were operated upon using a closed circuit/centrifugal pump system with coated surfaces (ISS) (SYNERGY, Stckert). Both groups did not differ regarding age, body mass, left ventricular function, number of bypasses, and concomitant diseases. Free hemoglobin (fHb), plasmin–antiplasmin complex (PAPc), platelet function (ROTEG), and interleukin 6 (IL-6) were measured preoperatively, intraoperatively (after sternotomy, during X-Clamp, during reperfusion, post ECC or ISS), and postoperatively. Technical problems were not observed. The ISS group demonstrated significantly less fHb during bypass, a lower intraoperative myocardial damage as well as less increase in IL-6 after bypass and postoperatively compared to ECC. In ISS fluid balance was significantly lower than in ECC whereas drainage loss and hospitalization did not differ statistically. Extracorporeal circulation with a closed circuit/centrifugal pump system can be routinely employed and appears to be safe. Intraoperative and early postoperative reduction of red blood cell trauma and inflammation are of potential value.
Key Words: Minimally invasive cardiopulmonary bypass
1. Introduction
ECC is still reported to evoke inflammatory reactions [1]. Blood exposure to artificial surfaces activates complement, leukocytes, and coagulation cascades [2]. Closed extracorporeal circulation has recently been developed to reduce deleterious effects of ECC [3]. This study compares the effects of a closed system with ECC on red blood cell damage, coagulation activation, fibrinolysis and cytokine expression to evaluate safety, efficacy, and clinical benefits of such a system.
2. Methods
Twenty patients underwent elective coronary revascularization for triple-vessel disease. All patients showed a low risk profile. Two groups (n=10) were defined: Standard ECC and ISS. The patients were randomly allocated to either system by means of envelopes opened by the perfusionist directly before the procedure. In all patients the LITA and a respective number of vein grafts were used.
The ISS is a device which integrates the functions of oxygenation, filtration, and air elimination in a compact manner in connection with a centrifugal pump.
When the air-eliminator sensor detects air a signal travels from the sensor to a control box so that the perfusionist can open an outlet. The tubing set is composed of custom 3/8 polyvinylchloride perfusion circuit coated with Phosphorylcholine (Phisio, Sorin). The total surface area of the circuit is <1.4 m2. The focus of development of this system has been to integrate primary functions of current ECC systems into a compact unit in order to reduce priming volume and foreign surface area.
In ISS patients arterial canulation was performed via the ascending aorta. A single tailored two-stage right atrial cannula (Stckert) was used for venous drainage. Air free venous connection was required. The initial priming volume in our setting was 950 ml, containing 850 ml electrolyte- solution, 1 million IU aprotinin and 5000 I.E. heparin versus 1850 ml in our standard ECC. Antegrade low-volume warm- blood cardioplegia (Calafiore) was administered in all patients. A cell saver system was used.
In each group blood samples were taken at the following 6 time points: preoperatively (I), intraoperatively (after sternotomy (II), 20 min postclamping (III), 10 min postdeclamping (IV), prior sternal closure (V), and 24 h postoperatively (VI). The following laboratory assessments were performed:
FHb as an important parameter to evaluate hemolytic anemia, especially intravascular hemolysis; Thrombin–antithrombin complex (TATc) as a marker of coagulation activation; Rotational thromboelastography (ROTEG Instrumantation, Germany) provides the viscoelastic measurement of clot strength in whole blood; Interleukin 6 (IL-6) as a potent mediator of the inflammatory; all Standard parameters.
Statistical analysis was performed using SPSS statistical package for Windows.
3. Results
Demographic data did not differ significantly between the groups (Table 1). Eighteen patients were male. As illustrated in Table 1, there were significant differences between ISS and ECC group with regard to duration of pump time and aortic cross-clamp time. In-hospital stay was lower for ISS patients, but without significance. All patients exhibited an uneventful course without significant complications. The detected Creatincinase- Mb-levels indicated a lower intraoperative myocardial damage in the ISS group than in the ECC group. The differences, however, disappeared after 24 h postoperatively [4].
The time course of IL-6 release in peripheral blood showed alterations. In the ECC group the noted increase was more rapid and the levels remained more elevated. However, only at time point V a significant difference was noted (P=0.003) ISS 17.3±11 pg/ml, ECC 46.4±23 pg/ml.
FHb showed a sharp increase during operation in ECC with a peak value more than fivefold higher than the only moderately elevated, corresponding levels of ISS patients. On POD 1 levels gradually dropped in both the ISS and the ECC group (Fig. 1).
There was a moderate intraoperative decrease of AT III levels noted in the ISS and the ECC group during the operation.
In both groups total platelets count did not react significantly. Data of the ROTEG did not reveal significant differences.
The surgeon's view towards the coronary vessels was not impeded by the absence of an active coronary vent. All operations with the ISS system were performed without detecting relevant air incorporation. Careful handling resulted in an amount of 250–380 ml blood concentrate for retransfusion after cell saver use.
4. Discussion
Different strategies to reduce inflammation during CABG have already been investigated: OPCAB; Coated systems comprising various inert substances [5,6]; pump optimization with centrifugal pumps [7].
The recently developed ISS is based on a concept of a short, closed circuit with coated surfaces. The present study demonstrated satisfactory clinical applicability of the new technique. Our results indicate that the use of the ISS system indeed resulted in a markedly reduced blood cell damage as well as a reduced alteration of the coagulation-cascade when compared with patients operated on ECC. These differences in activation of the coagulation pathway are remarkable because it has been demonstrated previously by Ovrum et al. [8] that a profound activation of coagulation through the interaction of blood with nonendothelial surfaces of the bypass circuit appeared to be inevitable.
IL-6 is a key mediator in the acute-phase response in infection. Elevation of plasma IL-6 level occurs both after cardiac operations with ECC [9] and after major noncardiac operations [10]. In our study a marked IL-6 response in the ECC group on the first postoperative day was noted to being higher than the values of the ISS group. This implies the induction of an intensified acute-phase response and suggests a greater degree of tissue trauma when using ECC.
In this pilot trial only patients with low comorbidities were involved. Therefore, clinical consequences of the alterations observed did perhaps not occur due to the maintained physiological compliance of these patients. We have encountered significant differences in the duration of cardiopulmonary bypass. Hence it is possible that the surgeon using ISS performed the procedure in a more alert and straightforward manner. Finally, the investigated cohorts were too small to obtain a reasonable clinical perspective.
Nevertheless, CABG with a closed system can be routinely employed and appears to be safe. Perioperative reduction of red blood cell trauma, coagulation disturbances and inflammation are of potential value.
References
Kirklin JK, Westaby S, Blackstone EH, Kirklin JW, Chenoweth DE, Pacifico AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983; 86:845–857.
Chenoweth DE, Cooper SW, Hugli TE, Stewart RW, Blackstone EH, Kirklin JW. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. New Eng J Med Feb 26, 1981; 304:497–503.
Abdel-Rahman U, zaslan F, Risteski PS, Martens S, Wimmer Greinecker G. Initial experience with a minimized extracorporeal bypass system: Is there a clinical benefit Ann Thorac Surg 2005; 80:238–244.
Immer FF, Pirovino C, Gygax E, Englberger L, Tevaearai H, Carrel TP. Minimal versus conventional cardiopulmonary bypass: assessment of intraoperative myocardial damage in coronary bypass surgery. Eur J Cardiothorac Surg 2005; 28:701–704.
Fromes Y, Gaillard D, Ponzio O, Chauffert M, Gerhardt MF, Deleuze P, Bical OM. Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation. Eur J Cardiothorac Surg Oct 2002; 22:527–533.
Albes JM, Sthr IM, Kaluza M, Siegemund A, Schmidt D, Vollandt R, Wahlers T. Physiological coagulation can be maintained in extracorporeal circulation by means of shed blood separation and coating. J Thorac Cardiovasc Surg 2003; 126:1504–1512.
Parolari A, Alamanni F, Naliato M, Spirito R, Franzè V, Pompilio G, Agrifoglio M, Biglioli P. Adult cardiac surgery outcomes: role of the pump type. Eur J Cardiothorac Surg 2000; 18:575–582.
Ovrum E, Brosstad F, Am Holen E, Tangen G, Abdelnoor M. Effects on coagulation and fibrinolysis with reduced versus full systemic heparinization and heparin-coated cardiopulmonary bypass. Circulation Nov 1, 1995; 92:2579–2584.
Ascione R, Lloyd CT, Underwood MJ, Lotto AA, Pitsis AA, Angelini GD. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg Apr 2000; 69:1198–1204.
Nijsten MW, DeGroot ER, Tenduis HJ. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Colch) 1990; 79:1611–1615.(Sren S. Just, Torsten Mül)