Brain Protection During Pediatric Cardiopulmonary Bypass

Improvements in peri‐ and postoperative surgical techniques have greatly improved outcomes for pediatric patients undergoing cardiopulmonary bypass (CPB) in the treatment of congenital heart defects (CHDs). With decreased mortality rates, the incidence of adverse neurological outcomes, comprising cognitive and speech impairments, motor deficits, and behavioral abnormalities, has increased in those patients surviving bypass. A number of mechanisms, including ischemia, reperfusion injury, hypothermia, inflammation, and hemodilution, contribute to brain insult, which is further confounded by unique challenges presented in the pediatric population. However, a number of brain monitoring and preventative techniques have been developed or are being currently evaluated in the practice of pediatric CPB. Monitoring techniques include electroencephalography, near‐infrared as well as visible light spectroscopy, transcranial Doppler ultrasound, and emboli detection and classification quantitation. Preventative measures include hypothermic perfusion techniques such as deep hypothermic circulatory arrest, low‐flow CPB, blood gas management, and pharmacologic prophylaxes, among others. The present review summarizes the principles of brain insult, neurodevelopmental abnormalities, monitoring techniques, methods of prevention, as well as preexisting morbidities and risk factors in pediatric CPB, with a focus on brain protection. Clinical and translational research is presented with the aim of determining methods that may optimize neurological outcomes post CPB and guiding further study.     

小儿体外循环期间血浆纤维粘接蛋白的变化

观察小儿体外循环心内直视手术转流前后血浆纤维粘接蛋白（ＰＦＮ）、血气值的变化，并分析影响ＰＦＮ的因素。结果表明，ＰＦＮ在转流期间水平最低，转流后ＰＦＮ仍无有意义回升。其原因可能与生成量下降、消耗量增加有关。故在小儿体外循环期间应采取相应措施减少转流中ＰＦＮ的消耗，以利在转流后尽快恢复。     

Granulocyte Superoxide Anion and Elastase Release During Cardiopulmonary Bypass

Abstract: Cardiopulmonary bypass (CPB) is known to induce several pathogenic responses in cardiovascular surgery. To explore leukocyte activation during PCB, we investigated superoxide anion (O₂^-) production by granulocytes in 6 patients undergoing aortocoronary bypass surgery. O₂^- production was determined with chemiluminescence amplified by a cypridina luciferin analogue. Granulocytes collected from the blood in the arterial site of the CPB circuit were stimulated by phorbol myristate acetate, n -formyl-methionyl-leucyl-phenylalanine, and opsonized zymosan. All the stimulators failed to disclose a significant difference between the magnitude of chemiluminescence during and after CPB. However, significant complement activation was detected, and the plasma level of granulocyte elastase increased gradually during and after CPB. This discrepancy between the unchanged O₂^- production by stimulated granulocytes and the increase in inflammatory mediators including granulocyte elastase may be due to sequestration of activated granulocytes in extravascular tissues. Namely, it was highly likely that activated granulocytes responsible for the increased plasma elastase level were sequestered and remained outside the blood circulation.     

Effect of Ultrafiltration During Cardiopulmonary Bypass for Pediatric Cardiac Surgery

The effect of ultrafiltration during cardiopulmonary bypass (CPB) was evaluated for correcting ventricular septal defects with associated pulmonary hypertension in patients less than 18 months old. Interleukin (IL)-6 and IL-8 concentrations in the blood, ultrafiltrate, and urine were measured. The blood IL-6 concentration increased to 128.4 ± 20.2 pg/ml by the end of surgery, which is lower than the concentration seen in adult patients (273.1 ± 48.2 pg/ml, p < 0.02). The blood IL-8 concentration was not significantly different than that of adults. The total amounts of excreted IL-6 in the ultrafiltrate and urine during CPB were 11.5 ± 0.32 pg/kg and 0.32 ± 0.07 pg/kg, respectively (p < 0.05). The total amounts of excreted IL-8 in the ultrafiltrate and urine were 4.64 ± 0.69 pg/kg and 1.92 ± 0.56 pg/kg, respectively (p < 0.05). No differences were seen in these values for excretion between children and adults. We conclude that ultrafiltration during CPB in pediatric patients is more effective in removing proinflammatory cytokines than in adults and more effective than renal filtration alone.     

Multisite Near Infrared Spectroscopy During Cardiopulmonary Bypass in Pediatric Patients

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty‐five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3–6) kg, 111 (47–203) days, and 0.24 (0.22–0.33) m², respectively. Median Aristotle score was 8 (6–10), and vasoactive inotropic score at CPB weaning was 16 (14–25). A total of 17 430 data points were recorded by each sensor: two‐way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80–90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.     

Minimizing Systemic Inflammation During Cardiopulmonary Bypass in the Pediatric Population

Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory response. Inflammation includes several cascade activations: complement, cytokine, and coagulation. The early phase is triggered by blood contact with the synthetic bypass circuit and the late phase by ischemia‐reperfusion and endotoxemia. Systemic inflammatory response syndrome (SIRS) is constant following cardiac surgery; however, a compensatory anti‐inflammatory response is also constant and the clinical manifestations (varying from uncomplicated SIRS to shock and multiple organ dysfunction) depend on the balance between the two responses. When overexpressed, the inflammatory response may significantly increase a patient's risk. Minimization of systemic inflammation is a major concern and several strategies aiming to inhibit the inflammatory response are described. None of them is satisfactory, but the “control” of the inflammatory response extent is likely to require a multimodal approach. This review aims to describe the strategies proposed to reduce CPB‐related systemic inflammation.     

婴幼儿心脏手术采用全胶体预充的临床观察

目的　观察婴幼儿心脏直视手术中 ,体外循环应用全胶体预充液对术中和术后液体平衡、出血和输血量的影响。　方法　收集全胶体预充前后先天性心脏病患者临床资料 15 1例 ,分别作为对照组和全胶体预充组 ,比较两组患者血液制品用量、胸腔引流液量、术中和术后液体出入情况以及临床恢复情况。　结果　全胶体预充组白蛋白用量多 ,术中超滤量、液体入量和尿量较少 ,术后速尿用量多 ;其余差别无显著性意义。　结论　婴幼儿体外循环全胶体预充有利于减少术中的液体入量     

Blood-Surface Interactions During Cardiopulmonary Bypass

A bstract The interaction between blood and the synthetic surfaces of the heart-lung machine activates plasma protein systems and blood cells to produce a host of vasoactive substances that mediate the "whole body inflammatory response" associated with cardiopulmonary bypass (CPB). Plasma proteins are instantaneously adsorbed onto nonendothelial surfaces; plasma factor XII is cleaved into two serine proteases; and platelets are activated to aggregate, adhere to adsorbed fibrinogen, and release granule contents. Activation of factor XII initiates coagulation by the intrinsic coagulation pathway and activates complement. Complement stimulates neutrophils to release vasoactive and cytotoxic substances. Endothelial cells, perhaps stimulated by formation of minute quantities of thrombin, produce tissue plasminogen activator, which generates plasmin, a fibrolytic enzyme. Blood becomes a stew of powerful enzymes and chemicals that alters vascular smooth muscle and endothelial cell contraction. Capillary permeability increases, fluid is retained, and function of essentially every organ is temporarily impaired. Attempts to control the morbidity of CPB have focused on reversible inhibitors of specific reactions in blood. Prostanoids and new disintegrins are promising platelet inhibitors that are reversible. Aprotinin and other serine protease inhibitors partially control fibrinolysis and activation of neutrophils. Alternatives to heparin also show promise. Eventually control of the interaction of blood and synthetic surfaces will control the adverse reactions of the heart-lung machine and reduce the bleeding, thrombotic and inflammatory complications of open heart operations.     

Myocardial Antioxidant Defenses During Cardiopulmonary Bypass

A bstract In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing super-oxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.     

Jugular Venous Oxygen Saturation During Mild Hypothermic Versus Normothermic Cardiopulmonary Bypass in Elderly Patients

Purpose. Age is known to be a major risk factor for adverse postoperative cognitive dysfunction after cardiac surgery. We conducted this study to determine if jugular venous oxygen saturation (SjvO₂) differed during mild hypothermic (32°C) and normothermic cardiopulmonary bypass (CPB) in elderly patients.Methods. Sixty patients aged over 70 years who underwent elective coronary artery bypass grafting were randomly divided into two groups. Group 1 (n = 30) underwent normothermic CPB (>35°C) and group 2 (n = 30) underwent mild hypothermic CPB (32°C). For the continuous monitoring of SjvO₂, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb after the induction of anesthesia. Hemodynamic parameters, and arterial and jugular venous blood gases were measured at seven time points.Results. The SjvO₂ in the normothermic group was lower at the onset of CPB and 20min after the onset, than from the time of induction of anesthesia until the start of surgery (period 1), the respective SjvO₂ values being 50.3% ± 1.0%, 50.1% ± 1.6%, and 59.5% ± 1.9% (P < 0.05). However, in the mild hypothermic group there were no changes in the SjvO₂ value throughout the study. The cerebral desaturation time (when the SjvO₂ value was <50%) and the ratio of the cerebral desaturation time to the total CPB time in the normothermic group differed significantly from those in the hypothermic group, being 19 ± 11min and 17% ± 10%, and 9 ± 3min and 8% ± 4%, respectively (P < 0.05).Conclusions. The SjvO₂ value was better during mild hypothermic CPB than during normothermic CPB in elderly patients.     

Enhanced Blood Conservation and Improved Clinical Outcome After Valve Surgery Using Heparin-Bonded Cardiopulmonary Bypass Circuits

Abstract Background: Recently, heparin-bonded (HBC) cardiopulmonary bypass circuits (CPB) were formed to be associated with improved outcome after coronary artery bypass grafting. There are very few reports on the efficacy and safety of these circuits in valve surgery. Methods: A retrospective cohort study of all patient populations undergoing first time valve surgery from 1992 to 1995 in a tertiary teaching hospital. Outcomes of 120 patients undergoing valve surgery using HBC and lower anticoagulation HBC were compared to 232 patients treated with conventional circuits and full heparinization (nonheparin-bonded-circuit [NHBC]). Results: Postoperative 24-hour chest tube drainage (558 ± 466 mL vs 1054 ± 911 mL, p < 0.00001), and reoperation for bleeding (2.5% vs 8.2%, p = 0.04) were lower in the HBC group. HBC patients required significantly less transfusions (total donor exposure of 6.9 ± 13.0 units vs 18.6 ± 26.2 units, p < 0.00001). Multiple linear regression analysis identified CPB time as a predictor of increased homologous blood transfusions, and the use of HBC, a large body surface area, and elective procedure as predictors of decreased transfusions. Perioperative mortality was similar (HBC 2.5%, NHBC 4.7%, p = 0.24). Overall complications were lower in the HBC group (42% vs 56.2%, p = 0.02). Perioperative myocardial infarction (0.8% vs 1.3%, p = 0.58) and cerebrovascular accident (3.3% vs 3.9%, p = 0.53) were similar. Two (1.7%) HBC patients had valve re-replacement compared to none in the NHBC (p = 0.22). Multiple logistic regression model revealed that age and CPB time were associated with increased complications, and the use of HBC with reduced complications. Conclusion: Use of HBCs with lower anticoagulation in valve surgery resulted in a significant reduction of transfusion requirements and improved clinical outcome. Because of a potential for early mechanical valve thrombosis, until further data is available, conventional levels of systemic anticoagulation should be achieved when using HBC in valve surgery.     

Impact of Distinct Oxygenators on Pulsatile Energy Indicators in an Adult Cardiopulmonary Bypass Model

The quantification of pulse energy during cardiopulmonary bypass (CPB) post‐oxygenator is required prior to the evaluation of the possible beneficial effects of pulsatile flow on patient outcome. We therefore, evaluated the impact of three distinctive oxygenators on the energy indicators energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) in an adult CPB model under both pulsatile and laminar flow conditions. The pre‐ and post‐oxygenator pressure and flow were measured at room temperature using a 40% glycerin‐water mixture at flow rates of 1, 2, 3, 4, 5, and 6 L/min. The pulse settings at frequencies of 40, 50, 60, 70, and 80 beats per minute were according to the internal algorithm of the Sorin CP5 centrifugal pump. The EEP is equal to the mean pressure, hence no SHE is present under laminar flow conditions. The Quadrox‐i Adult oxygenator was associated with the highest preservation of pulsatile energy irrespective of flow rates. The low pressure drop–high compliant Quadrox‐i Adult oxygenator shows the best SHE performance at flow rates of 5 and 6 L/min, while the intermediate pressure drop–low compliant Fusion oxygenator and the high pressure drop–low compliant Inspire 8F oxygenator behave optimally at flow rates of 5 L/min and up to 4 L/min, respectively. In conclusion, our findings contributed to studies focusing on SHE values post‐oxygenator as well as post‐cannula in clinical practice. In addition, our findings may give guidance to the clinical perfusionist for oxygenator selection prior to pulsatile CPB based on the calculated flow rate for the individual patient.     

Clinical Evaluation of New Generation Oxygenators With Integrated Arterial Line Filters for Cardiopulmonary Bypass

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group‐T) or Sorin Synthesis (40 patients, Group‐S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High‐sensitivity C‐reactive protein (hs‐CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between‐groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group‐P and group*time‐P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group‐T showed higher hs‐CRP (group‐P = 0.034), aPTT (group‐P = 0.0001), and INR (group‐P = 0.05), with lower serum albumin (group‐P = 0.014), total proteins (group‐P = 0.0001), fibrinogen (group‐P = 0.041), and PLTs (group‐P = 0.021). Group‐T also showed higher postoperative bleeding (group‐P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post‐CPB inflammatory response.