Effects of new polymer-coated extracorporeal circuits on biocompatibility during cardiopulmonary bypass

An inflammatory response due to bioincompatibility of extracorporeal circuits is a major clinical issue during cardiopulmonary bypass (CPB). By using a swine model, we determined whether new polymer-coated circuits, the blood-contacting surfaces of which are coated with poly(2-methoxyethylacrylate) (PMEA), would reduce the inflammatory response during CPB. Plasma bradykinin levels and the percentages of CD35-positive monocytes in PMEA-coated circuits were significantly lower than those in uncoated circuits during CPB. The amount of proteins adsorbed on the PMEA-coated circuits was significantly lower than that on the uncoated circuits (0.30 microg/cm2 versus 3.42 microg/ cm2). Almost no IgG, IgM, or C3c/d was detected in proteins adsorbed on the PMEA-coated circuits although these proteins were clearly detected in proteins adsorbed on the uncoated circuits. We concluded that PMEA coating could reduce complement activation during CPB by suppressing the adsorption of IgG and IgM, which activate C3 via the classical pathway, on the surface of the circuits.     

肝素涂层管道对体外循环中血小板的保护作用

目的：探讨常规剂量肝素体外循环（CPB）下使用肝素涂层CPB管道（HCC）对血小板的影响。方法：机械瓣膜置换术患者随机分为HCC组（n=8）和对照组（n=15）。分别在CPB前、CPB60min、肝素中和后30、60min及手术后12h测定血小板计数（PLT），血浆α颗粒膜蛋白－140（GMP－140）的浓度及手术后12h出血量。利用电子显微镜观察两组转流后微栓过滤网上沉积物的附着情况。结果；对照组PLC在转流中、后显著低于HCC组，差异有显著性（P＜0．05），且血浆GMP－140浓度在转流60min、转流中和后30、60min显著高于HCC组，差异有显著性（P＜0．05），但手术后12h差异无显著性（P＞0．05）；HCC组手术后12h出血量较对照组少，差异有显著性（P＜0．05）；HCC组动脉过滤网表面光洁，网眼边缘清晰，偶见白细胞和血小板附着；对照组动脉过滤网表面可见纤维蛋白沉积，网眼边缘模糊，有大量白细胞及少数活化血小板粘附。结论：HCC在CPB中对血小板具有保护作用，较好地改善CPB装置的血液相容性。     

Improving cardiopulmonary bypass: heparin-coated circuits

Heparin-coated circuits have been repeatedly proven to reduce the inflammatory response and foreign surface activation triggered upon initiation of cardiopulmonary bypass (CPB). In recent years, increasing numbers of studies are proving significant reductions in postoperative blood loss and transfusion requirements and improvements in clinical outcomes as a result of heparin-coated circuits. These results are promising steps in our efforts to improve CPB, as our patient population gets older and more complicated.     

A propensity score analysis on the effect of eliminating cardiopulmonary bypass for coronary artery bypass grafting

AIM: The aim of the study was to investigate if the off-pump technique could reduce the hospital mortality after coronary artery bypass grafting when compared to the standard cardiopulmonary bypass (CPB) technique. METHODS: An observational study with propensity score matching analysis was performed in a university teaching hospital in 2,899 consecutive patients undergoing elective coronary artery bypass grafting. No intervention was performed. Major perioperative complications and hospital mortality were noted. RESULTS: The overall hospital mortality was 1.3% (39/2,899) with no difference between the off-pump (16/802, 2.0%) and the CPB group (23/2,097, 1.1%) P=0.09. Since the off-pump group included patients at high risk, a propensity score analysis was then performed and off-pump patients matched 1:1 to CPB patients in order to have the same preoperative variables identified by a multivariate analysis as associated to surgeon propensity to operate off-pump: (age, chronic renal failure and low ejection fraction) and the same number of graft performed. The results of the propensity matching still showed no difference in hospital mortality between off-pump and CPB group (1.6% vs 1.1% P=0.6). The off-pump technique showed advantages in terms of transfusion of blood products (P<0.001) and reduction of surgical re-exploration (P=0.04). CONCLUSIONS: No difference in hospital mortality in coronary artery bypass grafting patients could be observed between patients operated off-pump or with the standard CPB technique.     

Heparin-bonded cardiopulmonary bypass circuits reduce cognitive dysfunction

OBJECTIVE: To determine the incidence of cerebral dysfunction in cardiac surgical patients exposed to heparin-bonded cardiopulmonary bypass (HB-CPB) versus nonheparin-bonded cardiopulmonary bypass (NH-CPB) circuits through neuropsychometric testing and to correlate these findings with markers of the systemic inflammatory response to CPB. DESIGN: Prospective, randomized, blinded clinical trial. SETTING: University hospital. PARTICIPANTS: Sixty-one patients undergoing elective cardiac surgery. INTERVENTIONS: A cohort of 61 patients scheduled for elective coronary artery bypass graft surgery were prospectively randomized to receive either HB-CPB or NH-CPB circuits during surgery. Patients were evaluated for cerebral injury using a battery of neuropsychometric tests at the following 3 time points: (1) before surgery as a baseline examination, (2) postoperative day 5, and (3) postoperative week 6. Blood samples were drawn to measure inflammatory markers at the following time points: (1) preincision, after induction of anesthesia, (2) 15 minutes after onset of CPB, (3) 30 minutes after CPB, (4) 6 hours postoperatively, and (5) 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Neuropsychometric performance was evaluated by group-rate and event-rate analyses. By group-rate analysis, patients undergoing surgery with HB-CPB performed significantly better at 5 days after surgery on 2 neuropsychometric tests (trails A [p < 0.01] and finger tapping with the dominant hand [p < 0.01]) and at 6 weeks after surgery on one neuropsychometric test (trails A [p < 0.01]). By event-rate analysis, at 5 days, patients undergoing surgery with HB-CPB circuits had less cognitive dysfunction (p < 0.05) compared with patients undergoing surgery with NH-CPB circuits. Serum samples were analyzed to evaluate markers of complement activation (C3a), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6), and coagulation (thrombin-antithrombin complex [TAT]) using the quantitative sandwich enzyme immunoassay technique. Although there were no significant differences in cytokine activation in either group, C3a was significantly higher in the NH-CPB group intraoperatively at 1 hour after CPB (p < 0.05), and TAT was higher in the HB-CPB group at 24 hours after surgery (p < 0.05). CONCLUSIONS: Patients undergoing cardiac surgery with CPB have less postoperative cognitive dysfunction during CPB when HB-CPB circuits are employed. Although there was a relationship, this finding did not correlate with decreased complement activation intraoperatively and activation of coagulation postoperatively.     

心肺转流国产型和进口型氧合器对丙泊酚血药浓度的影响

目的 探讨国产氧合器构成的心肺转流(CPB)回路对丙泊酚血药浓度的影响.方法 60例ASAⅡ或Ⅲ级择期在CPB下行心脏瓣膜置换术患者,随机均分为国产鼓泡组(A组)、国产膜肺组(B组)和进口膜肺组(C组).三组在麻醉诱导插管后,实施丙泊酚靶鞚输注(TCI),用反向高效液相法测定CPB前、CPB中1、5、10、20、40、60 min及停CPB后5、10 min时的丙泊酚血药浓度.结果 与CPB前比较,CPB 1 min时丙泊酚血药浓度A组下降22.6%,B组下降28.7%,但差异无统计学意义,C组明显下降31.1%(P＜0.05).B组丙泊酚浓度在CPB 20 min时恢复到CPB前水平,而A、C组在CPB 40 min时恢复到CPB前水平.三组之间丙泊酚血药浓度的差异无统计学意义.结论 尽管国产氧合器与进口氧合器一样对丙泊酚有吸附作用,但国产化的CPB回路对丙泊酚血药浓度无明显影响.     

Quantitative evaluation of heparin-coated versus non-heparin-coated bypass circuits during cardiopulmonary bypass

The extracorporealization of blood activates various elements of the fibrinolytic, coagulation, and complement systems. It is theorized that advancements in biocompatibility ameliorate many of the changes leading to improved patient management. The purpose of this study was to determine if heparin-coated circuit (HCC) utilization during cardiopulmonary bypass enhances patient outcomes in a cost-effective manner. A search of the English medical literature was completed to identify all clinical, prospective, randomized trials comparing HCC and non-HCC in patients undergoing coronary artery bypass grafting or valvular surgery. Twenty-six papers consisting of a sample size of 1515 patients were identified and included in the study parameters. The study distinguished between Duraflo II and Carmeda coating techniques and matched papers with different heparin loading doses, as well as use of a heparin-coated cardiotomy. Study parameters were matched for all papers and analyzed according to the availability of data. Statistically significant benefits of HCC were found in postoperative blood loss, time in the ICU, end bypass C3a, time to extubation, end bypass lactoferrin, and end platelet count, but not with respect to postoperative chest tube drainage, red blood cell transfusions, and end bypass TAT complex, D-dimers, and BTG. Data comparing the use of coated or uncoated cardiotomy utilization failed to demonstrate a benefit to heparin coating. Several immunological variables were ameliorated when Carmeda HCC was utilized, although data were insufficient to establish a cost-benefit analysis. In conclusion, heparin-coated circuitry provided statistically better results when compared to noncoated circuitry.     

Biocompatible circuits: an adjunct to non-cardiac extracorporeal cardiopulmonary support

The utilization of cardiopulmonary bypass systems, for circulatory and/or pulmonary support of patients undergoing non-cardiac procedures, has been previously reported. There is, however, a sub-group of patients for whom total systemic anticoagulation for cardiopulmonary support is extremely undesirable or contraindicated altogether, due to the presenting pathology or procedure to be performed. Clinical and experimental reports have suggested that with the use of heparin-bonded bypass circuits, the amount of heparin required for anticoagulation of the patient may be substantially reduced, or eliminated, safely. This allows the resuscitation and/or support of patients in whom bypass would otherwise be contraindicated. We present our clinical experience with heparin-bonded, biocompatible circuits, for support of patients undergoing non-cardiac procedures. In each case, low-dose or no heparin was administered. The group includes patients with trauma related pulmonary insufficiency, pulmonary embolism, hypothermia, neurosurgery, aortic aneurysm, aortic transection, respiratory distress syndrome, pericardiectomy, and cardiogenic shock.     

Experimental research with synthetic copolymer-coated cardiopulmonary bypass circuits: inflammatory and thrombogenicity analysis

This study aimed to assess complement system activation and index of thrombogenicity and platelet aggregation between synthetic copolymer-coated cardiopulmonary bypass (CPB) circuit and conventional CPB circuit. Twenty-six pigs were equally divided into two groups--the conventional group and the coated group. They were placed on CPB for 90 min, and blood samples were collected at three different time points (T0, right before CPB establishment; T1, 45 min after starting CPB; and T2, 90 min after starting CPB) to measure total count of inflammatory cells (leukocytes, neutrophils, lymphocytes, and platelets) and serum levels of fraction C3 of complement system. Upon completion of the 90-min CPB, fragments of different compartments of the CPB circuit were taken for assessing index of thrombogenicity and platelet aggregation. There were no differences between both groups regarding total count of leukocytes, neutrophils, and lymphocytes; however, there was a lower count of platelets at T2 in the coated group (P = 0.020). The serum level of fraction C3 was lower in the coated group at T1 (P = 0.020) and T2 (P = 0.017). Higher index of thrombogenicity and platelet aggregation were detected in the conventional group (77% of the animals within the conventional group) than in the coated group (46% of the animals within the coated group). In conclusion, in heart surgery requiring CPB, the use of synthetic copolymer-coated CPB circuit may be useful to reduce complement system activation, as well as attenuating index of thrombogenicity and platelet aggregation.     

Acute renal failure in coronary artery bypass surgery: independent effect of cardiopulmonary bypass

BACKGROUND: Acute renal failure after cardiac surgery is associated with a high morbidity and mortality, particularly when associated with hemodialysis. The aim of the study was to investigate whether the use of cardiopulmonary bypass increased the risk of developing acute renal failure. METHODS: The 2199 consecutive patients undergoing isolated coronary artery bypass grafting between January 2000 and March 2002 were retrospectively analyzed. Patients with significant preoperative renal dysfunction (preoperative serum creatinine > 200 micromol/L) were excluded. A multivariate logistic regression model was constructed to identify independent risk factors for the development of acute renal failure. RESULTS: In the study, 53 patients (2.4%) developed acute renal failure before hospital discharge. The crude incidences of acute renal failure for isolated coronary artery bypass grafting in the on- and off- pump groups were 2.9% and 1.4%, respectively (p = 0.031). There were 1483 patients who underwent on-pump surgery whereas 716 patients were in the off-pump group. The two groups were broadly comparable on many variables. The off-pump group were slightly younger on average (63.6 versus 64.9 years old [p = 0.017]), but had more angina class IV patients (39.5% versus 28.9% [p < 0.001]) and a greater proportion of redo surgery (4.1% versus 1.6% [p < 0.001]). The on-pump group had more patients with three-vessel disease (82.8% versus 74.3% [p < 0.001]). The logistic regression model identified use of cardiopulmonary bypass as an independent risk factor for the development of acute renal failure (odds ratio 2.64 [95% confidence intervals 1.27 to 5.45]). Other independent predictors of acute renal failure were preoperative creatinine levels, diabetes, emergency operations, increasing age, increasing body mass index, and peripheral vascular disease. CONCLUSIONS: Cardiopulmonary bypass is associated with significantly increased risk of acute renal failure following isolated coronary artery bypass surgery.     

Superior biocompatibility of heparin-bonded circuits in pediatric cardiopulmonary bypass

Background: Heparin bonding of pediatric cardiopulmonary bypass circuits may decrease activation of blood compartments as inflammatory responses. We studied the biocompatibility of heparin-bonded circuits in infant cardiac surgery.Methods: Twenty-four infants undergoing elective cardiac surgery were randomly assigned to either a nonheparin-bonded control circuit (n = 12) or a fully heparin-bonded circuit (n = 12) including membrane oxygenator, reservoir, and all tubing. Blood samples were used to identify differences in complement activation and cytokine release between groups during and after cardiopulmonary bypass. The postbypass oxygenation index was also compared.Results: The C3 activation product in the heparin-bonded group was significantly lower during (p < 0.01) and just after (p < 0.05) cardiopulmonary bypass. No statistically significant difference in C4 activation products was observed. Lower interleukin-6 and tumor necrosis factor-α were found immediately after cardiopulmonary bypass (p < 0.05) and a higher mean postbypass oxygenation index was also seen (p < 0.05) in the heparin-bonded group.Conclusion: We found that a heparin-bonded cardiopulmonary bypass circuit reduced inflammatory response and improved oxygenation in pediatric cardiac surgery. These results suggest that the superior biocompatibility of the bonded circuit may reduce pulmonary complications.     

体外循环中有效的肺动脉灌注方式

目的 探索方便、有效的肺动脉灌注模式,以缓解体外循环心脏术后肺损伤.方法 14只健康家犬模拟临床体外循环肺损伤特点建立动物模型,随机平均分为对照组及灌注组.体外循环期间,分别于实验肺缺血之初及再灌注之前,以15～20 mm Hg(1 mm Hg=0.133 kPa)的灌注压力短时间对灌注组动物实验肺实施改良低钾右旋糖酐保护液灌注;对照组动物无保护液灌注.90 min体外循环肺缺血后,再灌注4 h,行实验肺肺功能变化测定.结果 再灌注后,两组动物实验肺肺功能均有不同程度的恶化.对照组,再灌注后实验肺顺应性及氧合指数均有较大幅度的下降,分别为(30±4)%及(45±5)%,肺血管阻力指数明显上升,幅度为(76±7)%;与对照组比较,灌注组上述指标的变化幅度均明显降低,分别为[(12±2)%,t0.01/2,12=4.885,P＜0.01];[(19±2)%,t0.01/2,12=5.656,P＜0.01];[(28±3)%,t0.01/2,12=6.853,P＜0.01)].结论 应用肺动脉灌注方式可明显减轻体外循环过程中肺组织的损伤,保护肺功能;实验的灌注方式可望方便地应用于临床体外循环心脏手术过程,不会明显干扰既定手术进程.     

Superior biocompatibility of heparin-bonded circuits in pediatric cardiopulmonary bypass.

BACKGROUND: Heparin bonding of pediatric cardiopulmonary bypass circuits may decrease activation of blood compartments as inflammatory responses. We studied the biocompatibility of heparin-bonded circuits in infant cardiac surgery. METHODS: Twenty-four infants undergoing elective cardiac surgery were randomly assigned to either a nonheparin-bonded control circuit (n = 12) or a fully heparin-bonded circuit (n = 12) including membrane oxygenator, reservoir, and all tubing. Blood samples were used to identify differences in complement activation and cytokine release between groups during and after cardiopulmonary bypass. The postbypass oxygenation index was also compared. RESULTS: The C3 activation product in the heparin-bonded group was significantly lower during (p < 0.01) and just after (p < 0.05) cardiopulmonary bypass. No statistically significant difference in C4 activation products was observed. Lower interleukin-6 and tumor necrosis factor-alpha were found immediately after cardiopulmonary bypass (p < 0.05) and a higher mean postbypass oxygenation index was also seen (p < 0.05) in the heparin-bonded group. CONCLUSION: We found that a heparin-bonded cardiopulmonary bypass circuit reduced inflammatory response and improved oxygenation in pediatric cardiac surgery. These results suggest that the superior biocompatibility of the bonded circuit may reduce pulmonary complications.     

Unusual cause of femorofemoral cardiopulmonary bypass failure

A case of femorofemoral cardiopulmonary bypass failure in a patient undergoing an emergent operation because of acute aortic dissection is described. The importance of the accurate deduction of preoperative transesophageal echocardiography findings is emphasized.     

The impact of heparin-coated circuits on hemodynamics during and after cardiopulmonary bypass

This study was performed to investigate if heparin-coated extracorporeal circuits can reduce the systemic inflammatory reaction with the subsequent release of vasoactive substances during and after cardiopulmonary bypass. Fifty-one patients scheduled for coronary artery bypass grafting were perfused with either a heparin-coated or an uncoated circuit. During bypass the mean arterial pressure was maintained as near as possible to 60 mm Hg. Mediators for inflammation, hemodynamic, and oxygen parameters were determined during and after bypass. To reach the target mean arterial pressure in the first hour of bypass the pump flow in the uncoated group had to be increased (P<0.05), consequently the systemic vascular resistance index decreased (P<0.05). After bypass more inotropic support was necessary in this group to reach this pressure. In the coated group less bradykinin, complement activation, and elastase was generated during bypass (P<0.05). The results of this study suggest that heparin coating not only improves biocompatibility, but also ameliorates the hemodynamic instability during and after bypass.