"Inflammatory response to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass"

"Cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome that may contribute to postoperative morbidity and mortality. We investigated the in-flammatory responses to colloids compared to crystalloid priming in cardiac surgery patients with cardiopulmonary bypass. Thirty patients undergoing coronary artery bypass grafting (CABG) preparing for CPB were randomized into Ringer's solution (RS), 10% hydroxyethyl starch (HES) or 25% human albumin (HA) group. Serum concentrations of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β ), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured before CPB, at the end of CPB and 1, 6 and 12 h after CPB. Serum C-reactive protein (CRP) was determined pre-operatively and then daily for 2 days. Body-weight gain was significantly decreased on the day after surgery in the HES group than in the RS group. Volume priming in CPB for CABG patients using HA or HES preparation had less tendency for intense inflammatory response with lower levels of TNF-α, IL-1 β , IL-6 and higher levels of IL-10 compared to patients treated with RS. HES prime had lower levels of circulating CRP than in patients treated with HA or Ringer prime on the second post-operative day. Our data indicate that volume priming using colloid during CPB in CABG patients might exert beneficial effects on inflammatory responses."     

Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass

BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB.     

Plasma and urinary cytokine homeostasis and renal function during cardiac surgery without cardiopulmonary bypass

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.     

Cytokine secretion after cardiac surgery and its relationship to postoperative fever

A relationship between the inflammatory response to cardiopulmonary bypass (CPB) and fever after coronary artery bypass graft surgery (CABG) is assumed, but has not been studied. Therefore, we sought to assess the temporal pattern of cytokines' elevation and its association with post-CABG fever. In 355 primary elective CABG patients, serum cytokines (TNF-alpha, IL-1ra, IL-1beta, IL-6, and IL-8) were measured before surgery, at cessation of CPB and 2.5, 4.5, 24, and 48 h post-CPB. Fever was defined as a temperature >38 degrees C. TNF-alpha, IL-1beta and IL-8 peaked within the first 2.5 h after bypass, returning to near normal levels by 24h and increasing again by 48 h. IL-6 peaked early after bypass and remained elevated at 48 h. IL-1ra was elevated early, before returning to baseline by 24 h. Postoperative fever developed in 27% of patients. Increased IL-6 levels and male gender were significant predictors of fever (C-index=0.68; p=0.0003). No other cytokine showed a significant association with fever development. Of note is the previously undescribed bimodal pattern of cytokines' secretion after CABG. The association of fever with IL-6 levels suggests inflammatory mediation.     

乌司他丁对心肺转流下心脏手术患者炎症因子及认知功能的影响

目的:探索乌司他丁(UTI)对心肺转流(CPB)下心脏手术患者炎症因子及认知功能的影响。方法:选择自2010年5月至2014年9月我院收治的CPB瓣膜置换手术患者60例,按照随机数表法将患者分成对照组和观察组,每组30例。观察组患者在麻醉诱导后静脉泵入1.2×10~4U/kg UTI,在CPB结束前5 min从体外管道内给予0.6×10~4U/kg UTI,对照组患者给予等量的生理盐水。对比两组CPB前(T0)、CPB开始后1 h(T1)、CPB结束后1 h(T2)、术后4 h(T3)及术后24 h(T4)的血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-6/10(IL-6/10)、中性粒细胞弹性蛋白酶(NE)、星形胶质细胞S100蛋白的β亚型(S100β)、超氧化物歧化酶(SOD)和丙二醛(MDA),在术前1 d和术后7 d时,采用简易精神状态检查表(MMSE)对患者进行神经精神功能测试,并评价患者的术后认知功能障碍(POCD)的发生率。结果:与T0相比,两组患者T1-T4的TNF-α、IL-6、NE、S100β、MDA水平明显升高,且观察组显著低于对照组,而两组IL-10、SOD水平显著下降,观察组显著高于对照组(P0.05)。术后7d,两组患者MMSE评分均明显高于术前1 d,且观察组显著高于对照组(P0.05);观察组POCD的发生率明显低于对照组(P0.05)。结论:UTI可以有效降低CPB下行瓣膜置换术患者的炎症因子水平,并改善患者的POCD,对于临床用药具有指导意义。     

Interleukin 10 production in patients undergoing cardiopulmonary bypass: evidence of inhibition of Th-1-type responses

The cardiopulmonary bypass (CPB) procedure has long been associated with a generalized immunosuppression. To understand further the cytokine-mediated regulation of the complex physiological and immunological changes induced by CPB, the authors decided to investigate whether CPB affects the release of interleukin (IL)-10, as well as other cytokines, in correlation to the inhibition of T cell responses. Using phytohaemagglutinin (PHA) as mitogen and peripheral blood mononuclear cells (PBMC) isolated from patients undergoing CPB, we investigated whether this procedure has an effect on the secretion of different patterns of cytokines (Th1- and Th2-type) and PBMC proliferation. In all patients, CPB significantly enhances IL-10 and IL-6 production in resting and PHA-stimulated PBMC. On the other hand, IL-2 production, in response to PHA, was significantly diminished. Reduced IL-2 and enhanced IL-10 production were associated with a significant decrease in PBMC proliferation. Immunosuppression was also associated to lymphopenia, while neutrophil counts were significantly enhanced. These results show that after CPB there is a transient but clear unbalanced immune response demonstrated by a differentiated production of Th1- and Th2-type cytokines. The release of different patterns of cytokines observed after CPB may be helpful in understanding and preventing the development of infectious and immune complications in surgical procedure employing CPB.     

改良极化液治疗对体外循环患者多脏器功能的作用及机制

目的:探讨改良极化液治疗对体外循环(CPB)患者多脏器功能的作用及机制。方法:将40例心脏二尖瓣置换病人随机分为对照(CONTROL)组(19例)和改良极化液(GIK)治疗组(21例)。GIK组于麻醉诱导前经中心静脉给予改良极化液500ml,CON-TROL组给予相同量的平衡盐。分别于术前、术后12h、后24h测定心肌酶谱、肝功能、肾功能,并于术前、麻醉后、CPB15min、开放升主5min、CPB结束前、术后30min、6h、12h、24h采集血样,测定CRP、IL-1、IL-10、TNF-α、肾上腺素、糖皮质激素。结果:GIK组患者AST、CK、LDH、CK-MB、ALT、TBA、BUN、CR术后12、24h均低于CONTROL组;GIK组患者CRP、IL-1、TNF-α水平CPB期及术后均低于CONTROL组,IL-10水平高于CONTROL组;GIK组患者糖皮质激素水平在CPB结束及术后24h低于CONT-ROL组,GIK组患者肾上腺素水平高于CONTROL组。结论:围CPB期给予葡萄糖-胰岛素-氯化钾液(GIK)治疗可以提高患者早期多脏器功能,其机制可能与减轻了炎症反应及降低应激状态有关。     

Perioperative kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass

IntroductionEndothelial Specific Molecule-1 or endocan is a novel biomarker associated with the development of acute lung injury (ALI) in response to a systemic inflammatory state such as trauma. Acute Respiratory Distress syndrome (ARDS), a severe form of ALI is a devastating complication that can occur following cardiac surgery due to risk factors such as the use of cardiopulmonary bypass (CPB) during surgery. In this study we examine the kinetics of endocan in the perioperative period in cardiac surgical patients.MethodsAfter ethics approval, we obtained informed consent from 21 patients undergoing elective cardiac surgery (3 groups with seven patients in each group: coronary artery bypass grafting (CABG) with the use of CPB, off-pump CABG and complex cardiac surgery). Serial blood samples for endocan levels were taken in the perioperative period (T0: baseline prior to induction, T1: at the time of heparin administration, T2: at the time of protamine, T2, T3, T4 and T5 at 1, 2, 4 and 6 h following protamine administration respectively). Endocan samples were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis incorporated the use of test for normality.ResultsOur results reveal that an initial rise in the levels of serum endocan from baseline in all patients after induction of anaesthesia. Patients undergoing off-pump surgery have lower endocan concentrations in the perioperative period than those undergoing CPB. Endocan levels decrease following separation from CPB, which may be attributed to haemodilution following CPB. Following administration of protamine, endocan concentrations steadily increased in all patients, reaching a steady state between 2 and 6 h. The baseline endocan concentrations were elevated in patients with hypertension and severe coronary artery disease.ConclusionBaseline endocan concentrations are higher in hypertensive patients with critical coronary artery stenosis. Endocan concentrations increased after induction of anaesthesia and decreased four hours after separation from CPB. Systemic inflammation may be responsible for the rise in endocan levels following CPB.     

抑肽酶抑制体外循环中炎症反应的应用研究

目的:总结抑肽酶抑制体外循环心脏直视手术中炎性反应的研究和临床应用。方法:自2001年1月至11月,因心脏瓣膜病变而施行心脏瓣膜置换手术的患者随机分为研究组和对照组,术中应用抑肽酶的患者作为研究组。两组患者的体外循环、麻醉方法、预充液配制及手术方式间无差异。分别在体外循环前、中、后监测IL-6、IL-8和TNF-α变化。结果:两组患者CPB开始前的各炎性因子浓度间无显著性差异(P>0.05),而体外循环开始至结束后对照组患者的各炎性因子浓度均比研究组患者显著增加(P<0.05)。结论:抑肽酶能有效的抑制体外循环术中IL-6、IL-8和TNF-α的释放,减轻体外循环术后炎性反应的程度,这对促进患者术后恢复、减少术后并发症具有重要的意义。     

Plasma levels of alarmin HNPs 1–3 associate with lung dysfunction after cardiac surgery in children

Background

Early onset of lung injury is considerable common after cardiac surgery and is associated with increasing in morbidity and mortality, but current clinical predictors for the occurrence of this complication always have limited positive warning value. This study aimed to evaluate whether elevated plasma levels of human neutrophil peptides (HNPs) 1–3 herald impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).

Methods

Consecutive children younger than 3 years old who underwent cardiac surgery were prospectively enrolled. Plasma concentrations of HNPs 1–3 and inflammatory cytokines were measured before, and immediately after CPB, as well as at 1 h, 12 h, and 24 h after CPB.

Results

Thirty patients were enrolled, 18 (60%) of whom were infants. Plasma levels of HNPs 1–3 and the pro-inflammatory cytokine interleukin-6 (IL-6) significantly increased immediately after CPB (P?<?0.001), while IL-8 increased 1 h after the CPB operation (P?=?0.002). The anti-inflammatory cytokine IL-10 levels were also significantly elevated immediately after CPB compared with the baseline (P?<?0.001). The stepwise multiple linear regression analysis showed that the plasma HNPs 1–3 levels immediately after CPB was independent correlated with the declined lung function, as reflected by the PaO₂/FiO₂ ratio on the first 2 days after operation (for the first day: OR, ?1.067, 95% CI, ?0.548 to ?1.574; P?<?0.001; for the second day: OR, ?0.667, 95% CI, ?0.183 to ?1.148; P?=?0.009) and prolonged mechanical ventilation time (OR, 0.039, 95% CI, 0.005 to 0.056; P?=?0.011). Plasma levels of HNPs 1–3 and IL-10 returned to the baseline values, while IL-6 and IL-8 levels remained significantly higher than baseline 24 h after CPB (P?≤?0.01).

Conclusions

Elevated HNPs 1–3 levels immediately after CPB correlate with impaired lung function, and HNPs 1–3 could serve as a quantifiable early alarmin biomarker for onset of lung injury in infants and young children undergoing cardiac surgery with CPB.

     

The bioactive peptides salusins and apelin-36 are produced in human arterial and venous tissues and the changes of their levels during cardiopulmonary bypass

This study aimed to examine the effects of CPB on salusin-α, salusin-β and apelin-36 bioactive peptides in people who are planned to undergo coronary artery bypass graft (CABG) operation due to coronary artery disease and to explore whether these peptides are produced in human aortic, saphenous and arterial tissues. The study included age and BMI matched 15 patients who underwent CABG operation by CPB. In order to determine salusin-α, salusin-β and apelin-36 levels, venous blood samples were collected before induction of anesthesia (T1), before CPB (T2), 5min before the removal of cross-clamp (T3), 5min after the removal of cross-clamp (T4), upon arrival in the intensive care (T5), at postoperative 24th hour (T6) and 72nd hour (T7). Salusin and apelin expressions of the tissues were shown by immunohistochemical method. Peptide amounts of sera and tissues were measured using ELISA. Salusins production by vessels occurs in fibroblast cells of the media in the aorta and smooth muscle cells of the media in the LIMA and saphena. Apelin is produced by endothelial cells of the intima and fibroblast cells of the media in the aorta and by smooth muscle cells of the media in the LIMA and saphena. Changes in the levels of salusin-β and apelin-36 were significant during CPB. Salusin-α, salusin-β and apelin-36 are locally synthesized in the arteries and veins. Salusins and apelin-36 might be important markers in the CPB, and also that salusin-β was more specific in comparison to salusin-α.     

体外循环长时间转流535例临床估价

目的：介绍长时间体外循环管理的方法和经验。方法：我院自1984年至1995年12月共施行体外循环时间超过120分钟的心脏直视手术535例,其中男性345例,女性190例;年龄3～71岁．体表面积0．55～2．2平方米。双瓣替换术151例．二尖瓣替换术113例,法乐氏四联症107例,冠状动脉旁路移植术62例,主动脉瓣替换术30例．复杂畸形25例．其它47例。全组病例均采用中深度低温及中深度血液稀释,心肌保护采用灌注含钾冷停跳液。复跳后．适当延长辅助循环时间。术中采用血液超滤法,并尽可能采用搏动性血流,以确保重要脏器有充沛的血供。结果：全组病例中．体外循环时间为70～214分钟,心脏停跳时间72～230分钟。术中自动复跳209例．自动复跳率占39％。结论：在长时间体外循环心脏直视手术中．综合应用上述措施．可显著提高体外循环质量．增加手术成功率。     

犬体外循环模型建立及麻醉处理

目的建立CPB实验动物模型,加强围手术期麻醉管理,探索肺功能保护方法 ,以减少术后并发症的产生。方法 20只实验犬全部用于建立实验动物模型。丙泊酚复合麻醉后,开胸;全血肝素化后,连接体外循环管道开始体外循环,微量泵入丙泊酚50～150μg/（kg·min）维持麻醉;监测麻醉诱导前（T0）、气管插管即刻（T1）、CPB前即刻（T2）、降温至32.0℃（T3）、阻断主动脉前即刻（T4）、阻断主动脉后2min（T5）、开始复温即刻（T6）、停CPB即刻（T7）及停CPB后15min（T8）9个时间结点的鼻咽温度、平均动脉压（mean arterial pressure,MAP）及心率（heart rate,HR）。结果体外循环期间各时点鼻咽温度均低于T0及T2（P〈0.05）;T1、T2及体外循环期间各时点的MAP明显低于T0（P〈0.05）,体外循环期间各时点的MAP低于T2（P〈0.05）;T4的HR明显低于T0及T2（P〈0.05）。体外循环期间各时点MAP比较无统计学意义（P〉0.05）。结论犬体外循环模型建立的成败与手术技术和麻醉管理密切相关。     

Comparison of hydroxyl radical generation in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass

We measured the hydroxyl radical (√OH) generation in fourteen patients undergoing coronary artery bypass grafting (CABG), of whom seven patients underwent on-pump CABG with cardiopulmonary bypass (CPB) and seven patients underwent off-pump CABG without CPB. To detect √OH generation, we measured the urinary excretion of √OH products of creatinine (Cr), creatol (CTL; 5-hydroxycreatinine) and methylguanidine (MG) with HPLC using the one point sampling and collected urine during and after the operation. The urinary CTL value corrected urinary Cr value of on-pump CABG significantly increased about 3-5 times from the beginning of CPB to 4 h after operation compared to the baseline value before CPB in both the collected urine and the one point sampling urine. The urinary MG/Cr value in both groups did not change significantly. Significantly increased √OH generation was found during and soon after on-pump CABG.     

Combination of urinary kidney injury molecule-1 and interleukin-18 as early biomarker for the diagnosis and progressive assessment of acute kidney injury following cardiopulmonary bypass surgery: a prospective nested case–control study

The aim of this nested case–control study was to assess the combined use of urinary kidney injury molecule (KIM)-1 and interleukin (IL)-18 for acute kidney injury (AKI) after cardiopulmonary bypass surgery (CPB). From a cohort of 122 subjects who underwent CPB, serial urinary KIM-1 and IL-18 concentrations were determined in 30 AKI and 92 non-AKI patients. An increased level of urinary KIM-1 was associated with the occurrence of AKI, whereas an increased level of IL-18 was related to progressive AKI. The combination of these two biomarkers facilitates the early diagnosis and assessment of the likely progression of AKI after CPB.     

Leptin and soluble leptin receptor changes after pulmonary endarterectomy: relations to cortisol and cytokine network

Leptin is a hormone that regulates food intake. During inflammatory status, leptin may contribute to the anorexia and cachexia of infection. Pulmonary endarterectomy was used as a model of non-infectious cytokine network hyperstimulation. Leptin and soluble leptin receptor (SLR) were compared with evolution of cortisol and inflammatory cytokines in twenty-two patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy using cardiopulmonary bypass (CBP) and deep hypothermic circulatory arrest (DHCA). Leptin, SLR, cortisol, IL-beta, IL-6, IL-8, and TNFalpha concentrations in arterial blood were measured before/after sternotomy, last DHCA, separation from bypass, 12, 18, 24, 36, and 48 h after sternotomy. Mean duration of CPB was 338.2 min.; mean circulatory arrest time 39.9 min. The initial decline of leptin, SLR, TNFalpha, IL-6, and IL-8 was followed by an increase culminating 6-24 h after sternotomy. Leptin peak levels were detected 24 h after sternotomy (28.0 ng/ml, 21.9-37.6). IL-6 culminated after separation from CPB, IL-8 was highest 12 h after sternotomy. Leptin concentrations correlated with IL-6 (r=0.82), and TNFalpha (r=0.73). Large cardiovascular surgery caused a significant increase in serum leptin, indicating its acute regulation by stress factors. This effect may be secondary to the inflammatory response mediated via cytokine stimulation. Correlation between leptin and IL-6 indicates the role of IL-6 in leptin induction.     

Increases in leukocyte cluster of differentiation antigen expression during cardiopulmonary bypass in patients undergoing heart transplantation

Cardiopulmonary bypass (CPB) is essential in heart transplantation surgery. It is also used in coronary artery grafting surgery where it has been associated with a postoperative inflammatory response. This manifests as an increase in pro-inflammatory proteins like interleukin-8 and tumour necrosis factor alpha accompanied by increases in neutrophil populations and increased expression of cluster of differentiation (CD) antigens. The latter have been investigated using flow cytometry, which is limited to the measurement of three to four CD antigens simultaneously. We have developed a novel antibody array that can simultaneously measure the expression of 72 different CD antigens. The purpose of this study was to use this technology to measure CD antigen expression in patients undergoing CPB during heart transplantation. Twelve patients undergoing this operation were studied. A preoperative sample acted as an internal control while a second sample taken during CPB was the comparator. No previous studies have examined changes in CD antigen expression during heart transplantation. We report an increase in the expression of 10 different CD antigens across all patients between the two time points.     

Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation

Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.