"Orpheus" cardiopulmonary bypass simulation system

In this paper we describe a high-fidelity perfusion simulation system intended for use in the training and continuing education of perfusionists. The system comprises a hydraulic simulator, an electronic interface unit and a controlling computer with associated real-time computer models. It is designed for use within an actual operating theatre, or within a specialized simulation facility. The hydraulic simulator can be positioned on an operating table and physically connected to the circuit of the institutional heart-lung machine. The institutional monitoring system is used to display the arterial and central venous pressures, the ECG and the nasopharyngeal temperature using appropriate connections. The simulator is able to reproduce the full spectrum of normal and abnormal events that may present during the course of cardiopulmonary bypass. The system incorporates a sophisticated blood gas model that accurately predicts the behavior of a modern, hollow-fiber oxygenator. Output from this model is displayed in the manner of an in-line blood gas electrode and is updated every 500 msecs. The perfusionist is able to administer a wide variety of drugs during a simulation session including: vasoconstrictors (metaraminol, epinephrine and phenylephrine), a vasodilator (sodium nitroprusside), chronotropes (epinephrine and atropine), an inotrope (epinephrine) and modifiers of coagulation (heparin and protamine). Each drug has a pharmacokinetic profile based on a three-compartment model plus an effect compartment. The simulation system has potential roles in the skill training of perfusionists, the development of crisis management protocols, the certification and accreditation of perfusionists and the evaluation of new perfusion equipment and/or techniques.     

Heparin-coated circuits reduce the formation of TNFα during cardiopulmonary bypass

Background: Cardiopulmonary bypass (CPB) causes a systemic intlammatory response. TNFα, which is a major inflammatory mediator, has been found in the circulation during and after CPB. Although previous studies have shown that heparin coating of the extracorporeal circuits reduces complement and granulocyte activation, and the inflammatory response, the possible effect of heparin coating on TNFα formation and the inflammatory response has not been fully investigated.
Methods: Eighteen patients scheduled for coronary artery bypass grafting were divided randomly into two groups. One group of patients had extracorporeal perfusion using heparin coated circuits (HC group, n = 9). The other group had extra-corporeal perfusion using an identical circuit that was not coated (UC group, n = 9). Blood samples were drawn before, during, and after CPB for measurement of plasma TNFα, plasma IL-8, neutrophil count, and neutrophil elastase.
Results: Plasma levels of TNFα increased during CPB in the UC group but not in the HC group. Plasma concentrations of IL-8 increased similarly during and after CPB in both groups. Coating the circuits with heparin did not affect the levels of IL-8. In both groups, the neutrophil count increased after the release of the aortic cross clamp and remained elevated for three days. In the HC group, however, the increase of neutrophil count was significantly lower compared with the UC group. Plasma concentrations of neutrophil elastase were significantly increased during and after CPB in both groups. However, the levels of elastase were significantly lower at certain time points in the HC group.
Conclusion: From these observations, we conclude that heparin coating of the extracorporeal circuits reduces the TNFα formation during CPB, which may reduce neutrophil activation.     

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.     

Dynamic evaluation of fluid shifts during normothermic and hypothermic cardiopulmonary bypass in piglets

BACKGROUND: Edema, generalized overhydration and organ dysfunction commonly occur in patients undergoing open-heart surgery using cardiopulmonary bypass (CPB) and induced hypothermia. Activation of inflammatory reactions induced by contact between blood and foreign surfaces are commonly held responsible for the disturbances of fluid balance ("capillary leak syndrome"). We used an online technique to determine fluid shifts between the intravascular and the interstitial space during normothermic and hypothermic CPB. METHODS: Piglets were placed on CPB (fixed pump flow) via thoracotomy in general anesthesia. In the normothermic group (n=7), the core temperature was kept at 38 degrees C prior to and during 2 h on CPB, whereas in the hypothermic group (n=7) temperature was lowered to 28 degrees C during bypass. The CPB circuit was primed with acetated Ringer's solution. The blood level in the CPB circuit reservoir was held constant during bypass. Ringer's solution was added when fluid substitution was needed (falling blood level in the reservoir). In addition to invasive hemodynamic monitoring, fluid input and losses were accurately recorded. Inflammatory mediators or markers were not measured in this study. RESULTS: Cardiac output, s-electrolytes and arterial blood gases were similar in the two groups in the pre-bypass period. At start of CPB the blood level in the machine reservoir fell markedly in both groups, necessitating fluid supplementation and leading to a markedly reduced hematocrit. This extra fluid need was transient in the normothermic group, but persisted in the hypothermic animals. After 2 h of CPB the hypothermic animals had received 7 times more fluid as compared to the normothermic pigs. CONCLUSION: We found strong indications for a greater fluid extravasation during hypothermic CPB compared with normothermic CPB. The experimental model using the CPB-circuit reservoir as a fluid gauge gives us the opportunity to study further fluid volume shifts, its causes and potential ways to optimize fluid therapy protocols.     

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.     

Use of bivalirudin as an anticoagulant during cardiopulmonary bypass

Bivalirudin is a short-acting direct thrombin inhibitor that has been used in cardiac surgical patients with heparin-induced thrombocytopenia (HIT) or suspected HIT. Although no direct thrombin inhibitor is indicated for anticoagulation during cardiac surgery in patients with heparin-induced thrombocytopenia (HIT) or suspected HIT, use of heparin-alternatives are increasing as the awareness of HIT increases. Reports of anticoagulation with bivalirudin are sporadic, however, with variable dosing and management strategies. In this report, we describe our management techniques for cardiopulmonary bypass with bivalirudin based upon our personal experience. Although the reported clinical experience with bivalirudin in cardiac surgery is reviewed, operative techniques for the perfusionist/surgeon team are discussed in detail. We recognize that the use of bivalirudin during cardiopulmonary bypass is evolving and modifications of technique will undoubtedly occur as further data and experience accumulate.     

A heparin-coated circuit reduces complement activation and the release of leukocyte inflammatory mediators during extracorporeal circulation in a rabbit

Heparin coating modifies complement activation during extracorporeal circulation much more effectively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement activation and subsequently the release of leukocyte inflammatory mediators during extracorporeal circulation through a simplified circuit. We found in the heparin-coated group a significantly reduced complement hemolytic activity (CH50), remaining higher leukocyte numbers, significantly decreased release of beta-glucuronidase, and most strikingly a complete prevention of tumor necrosis factor (TNF) formation. The significantly reduced CH50 activity in the heparin-coated groups indicates the reduction of one or more native classical complement products. This could be explained by the absorption of complement components by the circuit, which results in reduced activity of the complement cascade. We conclude therefore that heparin coating reduces complement activation and consequently reduces the release of leukocyte inflammatory mediators.     

多巴胺对病人体外循环期间肾血流的影响

目的 评价小剂量多巴胺对病人体外循环(CPB)期间肾血流的影响.方法 择期体外循环下行心血管手术病人60例,年龄21～64岁,随机分为2组(n=30):生理盐水对照组(C组)和多巴胺组(D组).麻醉诱导后气管插管,机械通气,分别于首次灌注心脏停搏液后5 min(给药前)及颈内静脉输注多巴胺2/μg·kg-1·min-120min时(给药后)采用经食管超声测定左侧肾动脉内径及血流速度,计算左肾血流量和肾动脉阻力.结果 与C组比较,D组给药后肾动脉血流速度及血流量增加,肾动脉阻力下降(P<0.05),肾动脉内径差异无统计学意义(P0.05).结论 CPB中静脉输注小剂量多巴胺可增加肾大血流量.     

Evaluation of biocompatible cardiopulmonary bypass circuit use during pediatric open heart surgery

The contact of blood with nonbiological surfaces during cardiopulmonary bypass (CPB) induces a whole body inflammatory response and increases postoperative morbidity directly related to bleeding complications and end organ dysfunction. Methods to reduce these effects have included modification of extracorporeal circuits through biocompatible coating of disposables and the application of various pharmacological agents. Biocompatible coated surfaces are designed to mimic physiologic surfaces. This study was designed to ascertain the effects of using coated circuits during pediatric CPB. After Institutional Review Board approval and parent/guardian consent, patients undergoing CPB, weighing less than 15 kg, with target CPB temperatures more than 28 degrees C, were enrolled into the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2-methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n = 16). Those patients were retrospectively matched to control patients having the same congenital repair with respect to patient size, surgeon, anesthesiologist, bypass time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n = 16). CPB data collected included on-bypass platelet count, hematocrit (HCT), and CPB blood product use. Postprotamine data collected in the operating room included blood product use, time from initial protamine administration to chest closure, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Postoperative intensive care unit (ICU) data included blood product use, HCT, chest tube output, platelet count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4, 6, 12, and 24 hours. Other data collected included intubation time, length of time to chest tube removal, and length of ICU stay. Statistical significance (p < .05) was seen in units of platelets transfused postprotamine, ventilator peak inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2, 4, 6, and 12 hours postoperative. Several parameters approached statistical significance, including PRBC transfused postprotamine, time from protamine administration to chest closure, postoperative day 0 platelets transfused, and ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used safely during pediatric heart surgery, resulting in a decrease in postoperative blood product use, improved postoperative lung function, and a reduction in the time spent in the ICU.     

Postoperative treatment with low molecular weight heparin after right heart assist for coronary artery bypass grafting

Right heart assist (RHA) was used for coronary artery bypass grafting (CABG). We explored the affection of the coagulation system during surgery and evaluated two different antithrombotic treatments postoperatively. The pilot study comprised 14 patients. During surgery activated clotting time (ACT) was kept?>?200 sec. By random the patients were selected to different postoperative treatments. The control group received acetyl salicylic acid (ASA) 150 mg daily, the intervention group received ASA 150 mg daily and Low Molecular Weight Heparin (LMWH) 5000 IU×2 for three days. Serum levels of prothrombin fragment 1 and 2 (F 1?+?2), plasmin-antiplasmin product (PAP), anti-Xa activity and functional antithrombin (ATIII) were measured. During surgery there was no increase of F 1?+?2 or PAP. After protamin was administered there was a significant increase of F 1?+?2 but not in PAP during the next 6 hours. Postoperative antithrombotic treatment with LMWH seems to normalise F1?+?2 while ASA does not. ACT level?>?200 sec. seems sufficient for RHA-CABG surgery. Fibrinolytic agents are not necessary. It seems that postoperative LMWH treatment prevents increased thrombine formation. General recommendations with respect to antithrombotic treatment beyond ASA can not be made based on study.     

Strategies that improve renal medullary oxygenation during experimental cardiopulmonary bypass may mitigate postoperative acute kidney injury

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体外循环心脏手术患者术前对预先指示认知情况调查

目的了解体外循环下心脏手术患者术前对预先指示认知情况并分析其影响因素。方法方便抽取体外循环心脏手术患者172例,采用一般人口学资料问卷及预先指示认知问卷调查患者。结果 41.3%的患者听说过预先指示,60.5%的患者愿意接受预先指示。Logistic回归分析显示,影响患者是否接受预先指示的独立因素有:文化程度、医疗决策主体、医疗决策中谁的意见最重要、病情难以逆转或疾病晚期是否放弃治疗、生存质量重要还是生存时间重要、是否听说过预先指示、是否听说过生前预嘱、是否听说过预立医疗代理人(均P0.01)。结论体外循环心脏手术患者对预先指示的了解较少,但对预先指示持支持态度,提高患者对预先指示的认知水平有助于提高患者对预先指示的接受程度。     

Prevalence,Course and Impact of HLA Donor‐Specific Antibodies in Liver Transplantation in the First Year

The presence of preformed donor‐specific HLA antibodies (DSA) in liver transplant recipients is increasingly recognized; however, the prevalence of DSA and their impact on early allograft function remains unknown. We prospectively followed serum DSA levels of 90 consecutive liver transplant recipients from baseline to 4 months. Twenty recipients (22.2%) had preformed DSA. No antibody‐targeting treatments were undertaken. Seven days after transplantation, DSA levels decreased markedly in all but three patients. Day 7 protocol biopsies showed diffuse C4d deposition along the portal stroma, central vein, subendothelial and stromal space in the patients with persistent high DSA levels. The rate of acute cellular rejection was not significantly different in patients with DSA. The transaminase and bilirubin levels remained comparable during the first year despite the presence of DSA. The three patients with persistently high DSA levels continue to have normal allograft function. We conclude that in most cases, DSA disappear after liver transplant, however in rare instances where they persist, there is evidence of complement activation in the liver allograft, without significant clinical impact in the first year.     

肺动脉灌注低温肺保护液抑制肺内实质细胞凋亡的研究

目的　探讨体外循环中肺动脉灌注低温保护液对肺内实质细胞凋亡的影响。方法　将4 0例行法洛四联症根治术的患儿分为肺保护组和对照组 (各 2 0例 )。肺保护组体外循环期间肺动脉灌注低温肺保护液 ,对照组行常规法洛四联症根治术。 2 0例患儿 (两组各 10例 )术后取右下肺组织活检标本 ,原位末端标记免疫组化染色法检测肺内实质细胞凋亡情况。同时监测围手术期肺功能及临床指标。结果　肺保护组肺内实质细胞凋亡率为 (10± 2 ) % ,而对照组肺内实质细胞凋亡率为 (18± 7) % ,两者比较 ,差异有显著性 (t=- 2 95 ,P <0 0 5 )。肺保护组术后氧指数较对照组高 ,回ICU病房后 0、6和 12h均有显著差异 [分别为 (4 92± 172 )、(4 4 4± 10 4 )、(4 89± 5 8)mmHg和 (36 9± 12 6 )、(347± 10 7)、(340± 119)mmHg ,t =2 5 9,P <0 0 5 ;t=2 88,P <0 0 1;t =5 0 6 ,P <0 0 1];肺保护组呼吸机辅助通气时间短于对照组 [(15± 11)h和 (2 6± 15 )h ,t=- 2 76 ,P <0 0 1]。结论　肺动脉灌注低温保护液可抑制肺组织内实质细胞凋亡 ,减轻体外循环肺损伤     

Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial

ObjectivesThe aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia–reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).MethodsA total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS).ResultsNO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 ± 0.39 ng/mL versus 2.41 ± 0.55 ng/mL, respectively (P = .001). The CK-MB value was significantly lower in NO-treated group compared with the control group 24 hours after surgery: 47.69 ± 8.08 U/L versus 62.25 ± 9.78 U/L, respectively (P = .001); and the VIS was significantly lower in the NO-treated group 6 hours after the intervention.ConclusionsNO supply to the CPB circuit during CABG exerted a cardioprotective effect and was associated with lower levels of VIS and cardiospecific blood markers cTnI and CK-MB.     

The Significance of Donor‐Specific HLA Antibodies in Rejection and Ductopenia Development in ABO Compatible Liver Transplantation

The role of humoral alloreactivity in ABO‐compatible liver transplantation remains unclear. To understand the significance of donor‐specific HLA alloantibodies (DSA) in liver rejection, we applied the currently used strategy for detection of antibody‐mediated rejection of other solid allografts. For this purpose we reviewed the data on 43 recipients of ABO identical/compatible donor livers who had indication liver biopsy stained for complement element C4d and contemporaneous circulating DSA determination. Seventeen (40%) patients had significant circulating DSA in association with diffuse portal C4d deposition (DSA+/diffuse C4d+). These DSA+/diffuse C4d+ subjects had higher frequency of acute cellular rejection (ACR) 15/17 versus 13/26 (88% vs. 50%), p = 0.02, and steroid resistant rejection 7/17 versus 5/26 (41% vs. 19%), p = 0.03. Based on detection of the combination DSA+/diffuse C4d+, 53.6% of cases of ACR had evidence of concurrent humoral alloreactivity. Six of the 10 patients with ductopenic rejection had circulating DSA and diffuse portal C4d, three of whom (2 early and 1 late posttransplantation) developed unrelenting cholestasis, necessitating specific antibody‐depleting therapy to salvage the allografts. Thus, in ABO‐compatible liver transplantation humoral alloreactivity mediated by antibodies against donor HLA molecules appears to be frequently intertwined with cellular mechanisms of rejection, and to play a role in ductopenia development.