Effect of cardiopulmonary bypass on pulmonary clearance of adrenomedullin in humans

BACKGROUND: Adrenomedullin is a potent vasodilatory peptide and its plasma concentration increases after cardiopulmonary bypass. We analyzed the contribution of the lung to the disposition of adrenomedullin before and after cardiopulmonary bypass in humans. METHODS: Thirty-five patients undergoing cardiac surgery with cardiopulmonary bypass were studied. Bloods were sampled from the pulmonary artery and left atrium at the following times: prior to systemic heparinization, during pulmonary reperfusion and after cardiopulmonary bypass. Plasma concentrations of total and mature adrenomedullin were measured using an immunoradiometric assay kit specific for human adrenomedullin. Intermediate adrenomedullin was calculated as the difference between total adrenomedullin and mature adrenomedullin. RESULTS: Before cardiopulmonary bypass, mature and intermediate adrenomedullin concentrations were reduced by the pulmonary circulation by approximately 30% and 20%, respectively. However, these effects were not observed during pulmonary reperfusion. Mature, but not intermediate, adrenomedullin was reduced after cardiopulmonary bypass. Furthermore, pulmonary clearance quantity of mature adrenomedullin was significantly enhanced after cardiopulmonary bypass. CONCLUSION: These results indicate that cardiopulmonary bypass temporally impairs the pulmonary clearance of mature and intermediate adrenomedullin, but clearance of mature, not intermediate adrenomedullin is enhanced after cardiopulmonary bypass.     

Rupture of extra-corporeal circuit tubing during cardiopulmonary bypass

Roller pumps are widely used for cardiopulmonary bypass in developing nations by virtue of proven safety during several years of institutional use and cost effectiveness. However, careful adjustment of roller occlusion is needed because they are known to cause spallation, tubing wear, and the occasional incident of rupture of tubing in the extracorporeal circuit. Rupture of polyvinylchloride tubing in the pump raceway during repair of a ventricular septal defect in a 4-year-old child is discussed. The event was managed by exclusion and replacement of the defective tubing during a short period of arrest. Use of an inappropriate boot pump and failure to detect its inclusion in the bypass circuit was a significant departure from protocol. However, because occlusion settings and duration of perfusion were within acceptable limits, a manufacturing flaw could also have contributed to tubing failure, and the event may or may not have been averted by the use of larger tubing. In conclusion, this incident reiterates the need for adherence to established protocol during assembly of the pump and draws attention to the fact that tubing integrity is not a guarantee and vigilance is warranted to handle its failure.     

Thiopentone levels during cardiopulmonary bypass

Plasma total and unbound concentrations of thiopentone were investigated during exponentially decreasing infusions in seven patients undergoing cardiopulmonary bypass. Total plasma thiopentone concentrations reached a plateau (10.2, SD 2.1 micrograms/ml) soon after the initial bolus dose and commencement of the infusion. Concentrations were maintained until the onset of cardiopulmonary bypass, whereupon total plasma thiopentone concentration fell abruptly to 50.0 (SD 5.8) percent of the prebypass level. The unbound fraction of thiopentone increased from 16.6 (SD 1.9) percent before bypass to a maximum of 29.3 (SD 5.6) percent during bypass (p less than 0.01), decreased to 22.9 (SD 3.3) percent at the end of bypass (p less than 0.01), but was still elevated 5-7 hours later (20.5, SD 2.5 percent). The result of the changes in binding was a smaller decline in unbound thiopentone concentration at the onset of bypass to 76.4 (SD 15.7) percent of the prebypass level. Also, unbound levels returned to the prebypass level by the end of bypass, whereas total levels remained low.     

Ventricular fibrillation during cardiopulmonary bypass

Changes in ultrastructure after induced ventricular fibrillation were studied in the normothermic and nonhypertrophic canine heart using a transmural myocardial biopsy method. Comparisons were made between subendocardial and subepicardial layers by the quantitative evaluation of ultrastructural changes in mitochondria and glycogen granules. Slight abnormalities characterized by interstitial edema, mitochondrial derangement, contraction bands, swelling of capillary endothelium were demonstrated throughout the myocardium following ventricular fibrillation. The myocardium following ventricular fibrillation did not demonstrate differences in ultrastructure between the subendocardial and subepicardial layers. These pathologic fine structural changes were at least in part reversible. Quantification of ultrastructure showed that mitochondria and glycogen granules were well preserved. It was suggested that the myocardium following ventricular fibrillation may be less affected by the no-reflow phenomenon after restoring normal coronary circulation.     

Methylprednisolone fails to preserve pulmonary surfactant and blood-air barrier integrity in a porcine cardiopulmonary bypass model

BACKGROUND: Pulmonary inflammation after cardiac surgery with cardiopulmonary bypass (CPB) has been linked to respiratory dysfunction and ultrastructural injury. Whether pretreatment with methylprednisolone (MP) can preserve pulmonary surfactant and blood-air barrier, thereby improving pulmonary function, was tested in a porcine CPB-model. MATERIALS AND METHODS: After randomizing pigs to placebo (PLA; n = 5) or MP (30 mg/kg, MP; n = 5), animals were subjected to 3 h of CPB with 1 h of cardioplegic cardiac arrest. Hemodynamic data, plasma tumor necrosis factor-alpha (TNF-alpha, ELISA), and pulmonary function parameters were assessed before, 15 min after CPB, and 8 h after CPB. Lung biopsies were analyzed for TNF-alpha (Western blot) or blood-air barrier and surfactant morphology (electron microscopy, stereology). RESULTS: Systemic TNF-alpha increased and cardiac index decreased at 8 h after CPB in PLA (P < 0.05 versus pre-CPB), but not in MP (P < 0.05 versus PLA). In both groups, at 8 h after CPB, PaO2 and PaO2/FiO2 were decreased and arterio-alveolar oxygen difference and pulmonary vascular resistance were increased (P < 0.05 versus baseline). Postoperative pulmonary TNF-alpha remained unchanged in both groups, but tended to be higher in PLA (P = 0.06 versus MP). The volume fraction of inactivated intra-alveolar surfactant was increased in PLA (58 +/- 17% versus 83 +/- 6%) and MP (55 +/- 18% versus 80 +/- 17%) after CPB (P < 0.05 versus baseline for both groups). Profound blood-air barrier injury was present in both groups at 8 h as indicated by an increased blood-air barrier integrity score (PLA: 1.28 +/- 0.03 versus 1.70 +/- 0.1; MP: 1.27 +/- 0.08 versus 1.81 +/- 0.1; P < 0.05). CONCLUSION: Despite reduction of the systemic inflammatory response and pulmonary TNF-alpha generation, methylprednisolone fails to decrease pulmonary TNF-alpha and to preserve pulmonary surfactant morphology, blood-air barrier integrity, and pulmonary function after CPB.     

局部血管紧张素Ⅱ水平与核因子-κB、p38丝裂素活化蛋白激酶信号传导通路活化在人门静脉高压症脾静脉血管病变中的作用

目的 探讨血管紧张素Ⅱ(AngII)与核因子(NF)-κB、p38丝裂素活化蛋白激酶(p38MAPK)信号传导通路活化在人门静脉高压症(PHT)脾静脉血管病变中的作用及其机制.方法 PHT组为乙肝后肝硬化门静脉高压症患者26例;对照组选取因外伤性脾破裂行脾切除术患者10例.放免法(RIA)检测脾静脉中AngII水平;免疫组织化学法测定脾静脉中NF-κB、Phospho-p38蛋白的表达.蛋白免疫印迹法检测脾静脉及体外培养的脾静脉血管平滑肌细胞的NF-κB 、Phospho-p38蛋白的表达.结果 PHT组脾静脉组织AngII为(248.91±48.31)ng/L,显著高于对照组AngII为(143.35±36.45)ng/L(P<0.01).免疫组织化学和蛋白免疫印迹均显示PHT组脾静脉NF-κB 、Phospho-p38蛋白的表达较对照组明显增强.体外培养脾静脉血管平滑肌细胞(VSMC),AngII在1×10-8～1×10-6mol/L浓度范围内,AngII以浓度依赖性方式增加人脾静脉VSMC中NF-κB 、Phospho-p38蛋白的表达.结论 门静脉高压症时脾静脉组织AngII水平升高,NF-κB、Phospho-p38蛋白表达增加.AngII能激活脾静脉血管平滑肌细胞NF-κB、p38信号传导通路.门静脉高压症时AngII可能通过激活P38和NF-κB信号对传导通路门静脉高压症的形成和维持可能起重要作用.     

No effect of L-arginine supplementation on pulmonary endothelial dysfunction after cardiopulmonary bypass

BACKGROUND: Acetylcholine is an endothelium-dependent vasodilator through the L-arginine-nitric oxide pathway. After ischemia-reperfusion this effect is attenuated, also demonstrated in the pulmonary circulation after cardiopulmonary bypass. Administration of L-arginine has been shown to have a protective effect on endothelial function in reperfusion injury. The aim of the current study was to test the possible effect of L-arginine on the acetylcholine reactivity in the pulmonary circulation after cardiopulmonary bypass. METHODS: Thirty-five patients with ischemic and/or valvular heart disease were investigated in a randomized, double-blinded, placebo-controlled study. The patients were divided into three groups. Group 1: high dose L-arginine (n=10), group 2: low dose L-arginine (n=10), group 3: placebo, no L-arginine, (n=15). The acetylcholine reactivity was tested with measurements of pulmonary vascular resistance before surgery and 1, 2 and 3-4 h after cardiopulmonary bypass. RESULTS: After cardiopulmonary bypass an attenuation of the acetylcholine reactivity over time was observed in all groups, with no differences between groups. CONCLUSION: In the current study L-arginine had no protective effect on the pulmonary endothelium after cardiopulmonary bypass, measured as reactivity to an infusion of acetylcholine.     

Sevoflurane-induced malignant hyperthermia during cardiopulmonary bypass and moderate hypothermia

A 56-year old man was admitted for elective mitral valve repair and coronary artery bypass surgery due to mitral valve leakage and unstable angina. After induction of anaesthesia he developed a combined metabolic and respiratory acidosis. Different diagnosis were considered and we decided to treat the patient with dantrolene due to suspicion of malignant hyperthermia (MH). The patient received one dose of dantrolene 2,5 mg/kg during cardiopulmonary bypass (CPB) and a second dose of dantrolene 2,5 mg/kg during weaning from CPB. The first arterial blood gas sample taken in the intensive care unit showed relapse of the acidosis and we administered an infusion of 150 mg dantrolene over 3 hours. The patient gradually recovered without sequel and MH was verified by muscle biopsy testing.     

Argatroban for anticoagulation during cardiopulmonary bypass in an infant

Heparin induced thrombocytopenia (HIT) is a rare, but potentially life-threatening complication of heparin therapy. In patients with HIT, alternative means of anticoagulation are necessary. The authors present an infant with HIT who required anticoagulation during cardiopulmonary bypass for tricuspid valve excision in the treatment of bacterial endocarditis. The direct thrombin inhibitor, argatroban, was successfully used. Previous reports regarding the use of argatroban and other nonheparin anticoagulants for anticoagulation are reviewed and suggestions regarding argatroban dosing in infants are presented.     

Anaesthetic management of an insulin-dependent diabetic child during cardiopulmonary bypass

The management of an insulin-dependent diabetic child presenting for correction of complex congenital heart disease requiring cardiopulmonary bypass is described. A constant rate glucose infusion and variable rate insulin infusion, combined with frequent serum glucose measurements, allowed prompt response to the glucose alterations associated with surgery and cardiopulmonary bypass.     

体外循环下肺动脉栓塞的外科治疗

目的 探讨体外循环下肺动脉切开取栓和肺动脉内膜剥脱术治疗慢性肺动脉栓塞的方法、围术期处理经验，以提高慢性肺动脉栓塞外科治疗的安全性。方法 全组12例慢性肺动脉栓塞患者均在浅低温体外循环心跳中切开肺动脉取栓及肺动脉内膜剥脱术。结果 全组12例无一例近期死亡，其中1例活检为平滑肌肉瘤，术后化疗，2年后复查元复发，其余11例均为血栓，术后临床症状减轻，活动能力明显提高。结论 体外循环下肺动脉切开取栓和内膜剥脱术是治疗慢性肺动脉栓塞的安全、有效的方法。     

Monitoring microemboli during cardiopulmonary bypass with the EDAC quantifier

Gaseous emboli may be introduced into the bypass circuit both from the surgical field and during perfusionist interventions. While circuits provide good protection against massive air embolism, they do not remove gaseous microemboli (GME) from the bypass circuit. The purpose of this preliminary study is to assess the incidence of GME during bypass surgery and determine if increased GME counts were associated with specific events during bypass surgery. In 30 cases divided between 15 coronary artery bypass grafts and 15 valve repairs, GME were counted and sizedt the three locations on the bypass circuit using the EDAC" Quantifier (Luna Innovations, Roanoke, VA). A mean of 45,276 GME were detected after the arterial line filter during these 30 cases, with significantly more detected (p = .04) post filter during valve cases (mean = 72,137 +/- 22,113) than coronary artery bypass graft cases (mean = 18,416 +/- 7831). GME detected post filter were significantly correlated in time with counts detected in the venous line (p < .001). Specific events associated with high counts included the initiation of cardiopulmonary bypass, heart manipulations, insertion and removal of clamps, and the administration of drugs. Global factors associated with increased counts post filter included higher venous line counts and higher post reservoir/bubble trap counts. The mean number of microemboli detected during bypass surgery was much higher than reported in other studies of emboli incidence, most likely due to the increased sensitivity of the EDAC Quantifier compared to other detection modalities. The results furthermore suggest the need for further study of the clinical significance of these microemboli and what practices may be used to reduce GME incidence. Increased in vitro testing of the air handling capability of different circuit designs, along with more clinical studies assessing best clinical practices for reducing GME activity, is recommended.     

Efficacy of haemofiltration during cardiopulmonary bypass in paediatric open heart surgery

Purpose Haemofiltration is a useful method for removing fluid overload in paediatric patients undergoing open heart surgery. However, its role in reducing the inflammatory response to cardiopulmonary bypass (CPB) is still controversial. This study was undertaken to examine the efficacy of haemofilter in reducing the inflammatory response to CPB in paediatric patients undergoing open heart surgery. Methods We studied 20 paediatric patients undergoing open heart surgery with long duration CPB. In ten patients conventional methods of suppressing inflammation, like aprotinin and methylprednisolone were used and in the other ten patients, haemofiltration was added to the conventional methods. Inflammatory response was assessed by increase in total white blood cell counts and decrease in complement factor 3 (C3) levels. Patients were followed up in the intensive care unit. Result The fall in C3 concentration and increase in WBC counts was significantly more in conventional group (29.1% and 81% respectively) as compared to the haemofilter group (11.4% and 37% respectively). However, it did not reflect on any significant increase in postoperative PaO2, decrease in mechanical ventilation or ICU stay. Conclusion Use of haemofilter decreases the inflammatory response, but its clinical implication in postoperative period is still not clear.