Deleterious Effects Of Cardiopulmonary Bypass Research Articles

Percutaneous Closure of Postmyocardial Infarction Ventricular Septal Defect

Postinfarction ventricular septal defect remains an important complication for myocardial infarction. It is associated with high mortality and morbidity. Despite early surgical closure attempts, mortality remains about 19–49%. Percutaneous approach, especially in high surgical risk patients is a promising alternative to traditional surgical closure, thus avoiding the deleterious effects of cardiopulmonary bypass and the ventriculotomy. The Amplatzer P.I. Ventricular Septal Defect Occluder is a device specifically designed to percutaneously close these defects in adult patients. The results reported using this device are comparable (if not better) to those for surgical closure. Here, we review the experience using this device and depict in detail the technical aspects of the procedure.

Invited commentary

Invited commentary

Impact of off‐pump coronary artery bypass surgery on postoperative renal dysfunction: Current best available evidence (Review Article)

Renal dysfunction is a serious complication after coronary artery bypass surgery with cardiopulmonary bypass. Cardiopulmonary bypass-related non-pulsatile flow, hypothermia, haemolysis, systemic inflammatory reactions and emboli are mentioned as possible causes for this postoperative renal dysfunction. In an attempt to avoid these deleterious effects of cardiopulmonary bypass, off-pump coronary artery bypass surgery has been rediscovered. Resurgence of interest in off-pump coronary artery bypass surgery is associated with the expectation that avoiding deleterious effects of the cardiopulmonary bypass leads to better outcomes and possibly decreased costs and resource use. We are currently practising in an era of evidence-based medicine that mandates the prospective randomized controlled trial as the most accurate tool for determining a treatment benefit compared with a control population. The present review article attempts to evaluate the current best available evidence from randomized controlled trials on the impact of off-pump coronary artery bypass surgery on postoperative renal dysfunction.

Aprotinin in cardiac surgery

Aprotinin is a naturally occurring serine protease inhibitor that is being used with increasing frequency in cardiac surgery and beyond to reduce blood loss and the need for perioperative blood transfusion. Through inhibition of serine proteases such as plasmin, aprotinin significantly reduces fibrinolysis, thereby aiding hemostasis during surgical procedures. In addition, aprotinin interacts with other factors in the coagulation and fibrinolytic cascade, creating a hemostatic balance, without increasing the risk of thrombosis. These proven benefits are supplemented by the anti-inflammatory properties of aprotinin, which may help curb some of the deleterious effects of cardiopulmonary bypass. This article will review the discovery of aprotinin, its mechanism of action, dosing and adverse effects, and highlight the major recent trials demonstrating its efficacy.

Deleterious effects of cardiopulmonary bypass in coronary artery surgery and scientific interpretation of off‐pump's logic

Cardiopulmonary bypass (CPB) has been suggested to be a cause of complex systemic inflammatory response that significantly contributes to several adverse postoperative complications. In the last few years, off-pump coronary artery bypass grafting (OPCAB) has gained widespread attention as an alternative technique to conventional on-pump coronary artery bypass grafting (ONCAB). However, a degree of uncertainty regarding the relative merits of ONCAB and OPCAB continues to be a significant issue. Surgeons supporting off-pump surgery, state that the avoidance of the CPB leads to significantly reduced myocardial ischemia-reperfusion injury, postoperative systemic inflammatory response and other biological derangements, a feature that may improve the clinical outcomes. However, perfection in perioperative care, surgical technique and methods of attenuating the untoward effects of CPB has resulted in better clinical outcome of ONCAB as well. Possible reasons of these controversial opinions are that high-quality studies have not comprehensively examined relevant patient outcomes and have enrolled a limited range of patients. Some studies may have been too small to detect clinically important differences in patient outcomes between these two modalities. We present a review of the available scientific interpretation of the literature on OPCAB with regard to safety, hemodynamic changes, inflammation, myocardial preservation and oxidative stress. We also sought to determine from different reported retrospective and randomized control studies, the initial and the long-term benefits of this approach, despite the substantial learning curve associated with OPCAB.

Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: A pilot clinical study

Thrombocytopenia and platelet dysfunction are major mechanisms of cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and their combination administered directly into the oxygenator on platelet function, platelet-leukocyte interactions, and postoperative blood loss in patients undergoing coronary artery bypass grafting. Blood samples from 41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate were quantified by means of flow cytometry. Collagen and thrombin receptor-activating peptide-induced platelet aggregation in whole blood was analyzed by means of aggregometry. Both nitric oxide or iloprost attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin, microparticle formation, Mac-1 upregulation, and suppression of collagen-induced aggregation. Nitric oxide plus iloprost was significantly more effective in preventing thrombocytopenia, microparticle formation, and P-selectin translocation. Moreover, this treatment preserved thrombin receptor-activating peptide-induced aggregation, which was not rescued by single treatments. Both nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss. Nitric oxide plus iloprost reduced the deleterious effects of cardiopulmonary bypass, such as thrombocytopenia, platelet activation, platelet-leukocyte aggregate formation, and suppression of platelet aggregative responses. The reduced postoperative bleeding observed with this treatment suggests that this is a new and clinically feasible therapeutic option for patients subjected to cardiopulmonary bypass.

Innovative Surgical Strategies: Minimally Invasive CABG and Off-pump CABG.

Minimally invasive coronary artery bypass grafting (CABG) and off-pump coronary artery bypass grafting (OPCAB) have made up a significant facet of the recent attempts of surgical myocardial revascularization to evolve. Driven by an effort to limit the deleterious effects of cardiopulmonary bypass (CPB), along with a response to both the growing interests in performing procedures through smaller incisions and the successes of catheter-based therapies, these therapeutic options have found themselves moving into the future by resurrecting their past. Minimally invasive CABG is the procedure by which coronary grafting is performed through a small anterior thoracotomy, without the use of CPB. Although feasible, the inability to offer a more thorough degree of revascularization has limited the applicability of this procedure and, therefore, accounts for its overall minor contribution to the number of coronary revascularizations performed annually. Conversely, as the technical feasibility of performing complete revascularization without CPB has been achieved with OPCAB, its place as a mode of therapy remains uncertain. Several clinical trials have been performed to date with only a few being done in a prospective, randomized fashion. From this data has come a mix of information regarding either improvements or, at a minimum, no change in the rate of complications between CABG with, and without, CPB, while at the same time maintaining equivalent short-term graft patencies. The question remains, however, to which patient population is this approach to CABG optimal? Our practice has largely reserved OPCAB for those patients in whom manipulation of the aorta is considered not feasible due to severe calcification or in "high-risk" patients who are felt to be unable to tolerate the adverse physiologic effects of CPB. This makes up approximately 15% of our CABG population, roughly equal to the national average, with the remaining patients being revascularized with the assistance of CPB.

Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass

Background Intraoperative autologous blood withdrawal protects the pooled blood from the deleterious effects of cardiopulmonary bypass. Following reinfusion after cardiopulmonary bypass, the fresh autologous blood contributes to less coagulation abnormalities and reduces postoperative bleeding and the need for allogeneic blood products. However, few data have been available concerning the quality and potential activation of fresh blood stored at room temperature in the operating room. Methods Forty coronary artery bypass grafting patients undergoing a consistent intraoperative and postoperative autotransfusion protocol had a median of 1,000 mL of autologous blood withdrawn before cardiopulmonary bypass. After heparinization the blood was drained from the venous catheter via venous cannula into standard blood bags and stored in the operating room until termination of cardiopulmonary bypass. Samples for hemostatic and inflammatory markers were taken from the pooled blood immediately before it was returned to the patient. Results There was some activation of platelets in the stored autologous blood, as measured by an increase of β-thromboglobulin. Indications of thrombin formation, as assessed by plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 were not seen, and there was no fibrinolytic activity. The red blood cells remained intact, indicated by the absence of plasma free hemoglobin. As for the inflammatory response, the levels of the terminal complement complex remained stable, and the cytokines tumor necrosis factor-α and interleukin 6 levels were not increased during storage. The complement activation products increased minimally, but remained within normal ranges. Conclusions Except for slight activation of platelets, there was no indication of coagulation, hemolysis, fibrinolysis, or immunologic activity in the autologous blood after approximately 1 hour of operating room storage. The autologous blood was preserved in a condition of high quality, and retransfusion after cardiopulmonary bypass represents an uncomplicated and almost costless procedure for blood conservation.

Total arterial revascularization on beating heart: experience in 803 cases.

To avoid the deleterious effects of cardiopulmonary bypass, total arterial revascularization was performed on the beating heart, using an Octopus stabilizer, in this prospective study of 803 patients without selection bias. Single-vessel disease was present in 71 (9%) patients, double-vessel disease in 204 (25%), and triple-vessel disease in 528 (66%). An ejection fraction < 30% was found in 127 (16%) cases. Angiography was carried out before discharge in 204 (25%) patients. Grafts included left and right internal mammary arteries and the radial artery. There were 2,661 grafts placed with a mean of 3.31 grafts per patient (range, 1 to 6). Operative mortality was 0.5%. There was no postoperative stroke and few incidences of renal impairment, even in patients with chronic renal failure. Blood transfusion was not required in 558 (69%) patients. Mean hospital stay was 5.6 days. Overall angiographic patency was 98.6%. Total arterial revascularization on the beating heart was found to be safe, effective, and reproducible in almost all patients, with excellent short-term patency rates and minimal morbidity.

Pro: Standard CABG is the procedure of choice for myocardial revascularization

The standard CABG operation, which was developed by Favalaro and colleagues in 1967,1 has today reached the stature of being regarded as one of the best tested, most proved interventions of any type in the history of medicine. The standard CABG represents the gold standard of the first order against which any new approaches to coronary revascularization need to be critically compared. It provides a completely controlled surgical field, permits complete revascularization, produces excellent relief of angina, in both the short and long term, prolongs life in important subgroups and can improve left ventricular function in patients with impaired baseline function.2 Thus, standard CABG meets the goals that could reasonably be set for the surgical treatment of coronary artery disease. It is today being accomplished with excellent, reproducible results in surgical centers all over the world. It can be performed by the average cardiac surgeon and has the lowest operative mortality and morbidity of any operation for ischemic heart disease. It goes without saying that a major surgical endeavor like CABG has some adverse effects. But over the decades it has become evident that cardiopulmonary bypass (CPB) is generally well tolerated. Devastating complications are rare and most adverse effects are mild and recoverable. The concept of off-pump CABG (OPCAB) is not new. It was described in 19673 and continued to be performed by a few surgeons. With CPB becoming more safe and refined, OPCAB became nearly obsolete. However, in recent years, there has been an upsurge of interest in OPCAB in an attempt to avoid the deleterious effects of CPB. Enthusiasts for OPCAB emphasize broad views on the systemic inflammatory response, neurologic and renal damage and cost benefits. This importance of cost control in medicine has become a driving force in the pursuit of alternatives to standard CABG. OPCAB is now possible. But is it better? There is no consensus. This article examines a number of pertinent issues regarding comparative merits and demerits of the standard CABG and OPCAB. For the purposes of the current discussion, standard CABG will be compared with the technique of performing CABG using a midline sternotomy but without the use of CPB.

Double lung transplantation via median sternotomy and with cardiopulmonary bypass is safe and without adverse clinical outcome

Background: The potential deleterious effects of cardiopulmonary bypass (CPB) have led many surgeons to adopt a no-bypass approach for bilateral lung transplantation via either bilateral sequential thoracotomies or a clamshell incision. In this study we have reviewed all our double lung procedures, regardless of disease classification, to assess the influence of CPB on clinical outcome.

Optimizing response of the neonate and infant to cardiopulmonary bypass

Abstract Despite the ability to surgically correct complex defects in neonates and infants, limitations in outcome are sometimes encountered in relation to exposure to cardiopulmonary bypass (CPB). The deleterious effects of CPB in neonates are often pronounced because of their immature tissue/organ function and the disparity between the CPB circuit size and the patient. A variety of techniques that have been developed to prevent or lessen tissue edema, including miniaturization of the circuit and oxygenator, prime additives (eg, albumin, steroids), biocompatible circuitry, and variations in perfusion strategies, are discussed as are post-CPB strategies such as modified ultrafiltration, which removes inflammatory mediator-rich fluid from the patient and bypass circuit. With optimization of the response of the infant to our systems used during repair of their cardiac lesion, we will see significant improvement in surgical outcomes. Copyright 2003 Elsevier, Inc. All rights reserved.

Optimizing response of the neonate and infant to cardiopulmonary bypass.

Despite the ability to surgically correct complex defects in neonates and infants, limitations in outcome are sometimes encountered in relation to exposure to cardiopulmonary bypass (CPB). The deleterious effects of CPB in neonates are often pronounced because of their immature tissue/organ function and the disparity between the CPB circuit size and the patient. A variety of techniques that have been developed to prevent or lessen tissue edema, including miniaturization of the circuit and oxygenator, prime additives (eg, albumin, steroids), biocompatible circuitry, and variations in perfusion strategies, are discussed as are post-CPB strategies such as modified ultrafiltration, which removes inflammatory mediator-rich fluid from the patient and bypass circuit. With optimization of the response of the infant to our systems used during repair of their cardiac lesion, we will see significant improvement in surgical outcomes.

Developmental and neurologic outcomes late after neonatal corrective surgery

J Thorac Cardiovasc Surg 2002;124:425-7

Heparin-bonded circuits without a cardiotomy: a description of a minimally invasive technique of cardiopulmonary bypass.

The deleterious effects of cardiotomy suction have been well recognized and well documented for some time. The use of cardiotomy suction results in the exposure of blood to the defoaming sock, aspiration of stagnant pericardial blood into the systemic circulation, and the entrainment of both fatty and gaseous microemboli. The purpose of this paper is to describe a technique using heparin-bonded cardiopulmonary circuits (HBCs) without the use of a cardiotomy reservoir or cardiotomy suction. Our group has previously demonstrated improved clinical outcomes using HBCs and a low-dose anti-coagulation protocol. It is our goal to further improve clinical outcomes and further attenuate the deleterious effects of cardiopulmonary bypass by eliminating the potential complications attributed to the use of cardiotomy suction.

Deep hypothermic circulatory arrest: Current status and indications

A number of groups have directed clinical and laboratory research efforts to define and delineate the limits of hypothermic circulatory arrest. The deleterious effects of cardiopulmonary bypass in small children are reviewed to place into historical perspective the impetus behind the development of hypothermic circulatory arrest. Among the advantages of deep hypothermic circulatory arrest are decreased exposure to cardiopulmonary bypass with its sequelae, improved operative field exposure, avoidance of multiple cannulas, and reduced postoperative edema. Because of concern regarding the effectiveness of the neurologic protection afforded by deep hypothermic circulatory arrest, a body of literature has developed that includes both clinical (eg, the Boston Circulatory Arrest Study) and laboratory investigations of the influence of pH strategy, hematocrit level, oxygen strategy, intermittent reperfusion, and their interaction on outcome measures. Concomitantly, changes in both cardiopulmonary bypass and circulatory arrest techniques have led surgeons to reconsider the indications for deep hypothermic circulatory arrest use in children. In the future it will be important to focus an equal degree of attention to refine methods of continuous cardiopulmonary bypass including innovative methods that allow avoidance of circulatory arrest. No clear guidelines are presently available for the congenital surgeon regarding how low flow can be reduced, at what temperature repair should be undertaken, and what duration of low flow can be used for particular circumstances of pH, hematocrit, and collateral return. Until this information is collected, the comprehensive information regarding circulatory arrest that has already been gathered allows this technique to be used more safely than innovative but unproven methods of continuous cardiopulmonary bypass. Copyright © 2002 by W.B. Saunders Company

Anti-inflammatory pre-treatment and the resultant effects of interleukin-10: adjuncts to multi-therapeutical strategies.

With the advent of off-pump coronary bypass surgery, there is increasing demand for research in attenuating the deleterious effects of cardiopulmonary bypass (CPB). An improved understanding of the systemic inflammatory response syndrome (SIRS) has distinguished which areas of components have the most adverse effects and which are, in fact, anti-inflammatory. This classification of inflammatory components allows strategic treatment for those likely to cause the most clinically significant 'effect', suitably termed 'effectors'. This article will identify current methods in treating 'effectors', as well as those components having anti-inflammatory effects. This article selectively features certain inflammatory components by: (1) grouping them as being 'mediators' or 'effectors'; (2) relating them to interleukin-10 (IL-10) and treatments potentiating anti-inflammatory effects; (3) summarizing their mechanisms of action; (4) recognizing the time periods during bypass exhibiting peak levels; and (5) investigating current treatment. methods and identifying their significance to 'effectors'. A literature search in MEDLINE was performed, featuring articles of the English-language within the past 5 years. Because of the characteristic of having interlinked multi-component cascades, it is evident that treating SIRS with a one-dimensional method would be inadequate. This article not only confirms the importance of a multi-factorial therapeutic approach, but also targets the inflammatory components having the highest potential for causing direct tissue damage, known as 'effectors'. In addition, previous studies have found IL-10 to have 'regulatory effects' during periods of excessive pro-inflammatory stimuli. These findings may arouse new ideas in exploring the area of anti-inflammatory cytokines. In fact, future treatments may suggest a new classification featuring 'mediators', 'effectors', and 'regulators'.

Effects of phentolamine on tissue perfusion in pediatric cardiac surgery

Objective: To evaluate whether the deleterious effects of cardiopulmonary bypass (CPB) can be overcome by phentolamine-induced pharmacologic vasodilation in pediatric patients with congenital heart disease. Design: Prospective, randomized, clinical study. Setting: Single university hospital. Participants: Forty-three pediatric patients undergoing open cardiac surgery for repair of congenital heart disease. Interventions: Patients were randomly allocated into two groups. Patients in group 1 (n = 22) received 0.2 mg/kg of phentolamine during the cooling and rewarming periods of CPB. Group 2 patients (n = 21) did not receive phentolamine. Temperature measurements (rectal [R], nasopharyngeal [N], and toe [P]) and serum lactate values were obtained before, during, and after CPB; systemic oxygen consumption was evaluated during CPB. Measurements and Main Results: At the end of the CPB period and at the end of the operation, lactate values of group 1 (1.87 ± 0.37 and 1.8 ± 0.39 mmol/L, respectively) were significantly lower than values of group 2 (2.24 ± 0.28 and 2.33 ± 0.33 mmol/L; p < 0.05 and p < 0.05, respectively). At the beginning of the rewarming period N-R temperature gradients of group 1 (0.14°C ± 0.92°C) were lower than group 2 (−0.58°C ± 1.84°C) values ( p < 0.05). Central-peripheral temperature gradients of group 1 obtained at the end of the CPB period (N-R = 2.18°C ± 0.69°C; N-P = 7.84°C ± 1.54°C; R-P = 5.66°C ± 1.70°C) were significantly lower than the values of group 2 (N-R = 2.80°C ± 0.91°C, N-P = 9.97°C ± 2.02°C; R-P = 7.18°C ± 2.10°C; p < 0.05; p < 0.001; p < 0.05). At the end of the operation values of group 1 (N-R = 0.48°C ± 0.31°C; N-P = 6.30°C ± 1.23°C; R-P = 5.82°C ± 1.16°C) were significantly lower than the values of group 2 (N-R = 0.94°C ± 0.56°C; N-P = 8.69°C ± 0.28°C; R-P = 7.75°C ± 2.15°C; p < 0.05; p < 0.001; p < 0.001). The systemic oxygen consumption values of group 1 were higher than group 2 (6.26 ± 1.82 v 5.17 ± 1.05 mL/min/kg; p < 0.05) after complete rewarming. Mean arterial pressure (MAP) values of group 1 (58.9 ± 6.4 mmHg) were lower than group 2 (63.4 ± 6.7 mmHg) at the period after CPB ( p = 0.03). Conclusion: The results suggest that the use of phentolamine during CPB is associated with limited systemic anaerobic metabolism and more uniform body perfusion.

Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin.

Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass. Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed for a 120-min period. In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05). The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies

Background. Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. Methods. Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). Results. Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation ( p = 0.00001), leukocyte filtration blunted postpump leukocytosis ( p = 0.043), and the aprotinin group had less fibrinolysis ( p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction ( p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day ( p = 0.02) and mean charges by $2,000 to $6,000 ( p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days ( p = 0.02) and mean charges by $6,000 to $48,000 ( p = 0.0007). Conclusions. These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.