Protein C -1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis

OBJECTIVE: Protein C contains an A/G polymorphism at position -1641 and a C/T polymorphism at -1654 associated with risk of deep venous thrombosis. We tested the hypothesis that these polymorphisms are associated with altered outcome in patients having severe sepsis, in which protein C is a central molecule. DESIGN: Prospective cohorts, gene-association study. SETTING: Tertiary care medical/surgical intensive care unit. PATIENTS: We first recruited a derivation cohort of patients having severe sepsis (n = 62). A second replication cohort was similarly defined but larger (n = 402). We tested for biological plausibility in a third cohort of post-cardiopulmonary bypass patients (n = 61). INTERVENTIONS: Patients were genotyped at protein C -1641 and -1654. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was survival in cohorts 1 and 2 and postoperative serum interleukin-6 concentration in cohort 3. Severity of individual organ dysfunctions and systemic inflammation were secondary outcome variables. In the first derivation cohort, the protein C -1641 AA genotype was associated with decreased 28-day survival (p < .05). This finding was confirmed in the much larger replication cohort of patients having severe sepsis (p = .028). In addition, the protein C -1641 AA genotype was associated with significantly more organ dysfunction and more clinical evidence of systemic inflammation (p < .05). Furthermore, the -1641 AA genotype was associated with increased serum interleukin-6 at 4 and 24 hrs after cardiopulmonary bypass (p = .024). There was no association of -1654 A/G with phenotype in any cohort. CONCLUSIONS: Protein C -1641 AA genotype is associated with decreased survival, more organ dysfunction, and more systemic inflammation in patients having severe sepsis and with increased interleukin-6 levels after cardiopulmonary bypass surgery.     

体外循环心脏瓣膜置换术对QT离散度的影响

目的探讨体外循（CPB）心脏瓣膜置换术对心肌QT离散度（QTd）的影响。方法记录30例心脏瓣膜置换术患者术前、术后第1天和术后第3天同步12导联心电图,观察各时间点QTd值和QT离散度校正值（QTcd）的变化。结果术后第1天及第3天QTd和QTcd较术前显著延长,以术后第1天最显著（P〈0．01）。术后发生室性心律失常者QTd均〉80ms。结论CPB心脏瓣膜置换术后QTd与QTcd明显延长,提示术后心肌复极不均一性增加,与手术、麻醉有关。QTd有可能作为预测CPB心脏手术后室性心律失常的指标。     

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.     

Doxazosin in metabolically complicated hypertension

Coronary artery bypass grafting (CABG) performed with cardiopulmonary bypass has become a well-established treatment modality for patients with coronary artery disease. However, there is increasing evidence that cardiopulmonary bypass may be responsible for some of the morbidity associated with CABG surgery. Thus, it has been proposed that CABG surgery would be safer if cardiopulmonary bypass could be avoided. The development of cardiac stabilization devices has allowed for the creation of safe and reproducible coronary anastomoses on the beating heart. Several large, non-randomized, retrospective case series have demonstrated that CABG surgery can be performed safely without cardiopulmonary bypass (off-pump) and have in fact suggested benefits when compared with conventional CABG. However, the randomized controlled studies published to date have, as a whole, been unable to conclusively demonstrate the advantages of off-pump surgery. Taken together, the evidence to date suggests that a large-scale, prospective, randomized trial may be required to resolve the dilemma.     

Off-pump coronary artery bypass graft surgery: where should we stand?

Coronary artery bypass grafting (CABG) performed with cardiopulmonary bypass has become a well-established treatment modality for patients with coronary artery disease. However, there is increasing evidence that cardiopulmonary bypass may be responsible for some of the morbidity associated with CABG surgery. Thus, it has been proposed that CABG surgery would be safer if cardiopulmonary bypass could be avoided. The development of cardiac stabilization devices has allowed for the creation of safe and reproducible coronary anastomoses on the beating heart. Several large, non-randomized, retrospective case series have demonstrated that CABG surgery can be performed safely without cardiopulmonary bypass (off-pump) and have in fact suggested benefits when compared with conventional CABG. However, the randomized controlled studies published to date have, as a whole, been unable to conclusively demonstrate the advantages of off-pump surgery. Taken together, the evidence to date suggests that a large-scale, prospective, randomized trial may be required to resolve the dilemma.     

The role of lactate acidosis and enzyme hyperactivity in evaluating hypoxic organ disorders in patients following cardiopulmonary by?ass]

One hundred and fifty patients after cardiopulmonary bypass surgery have been examined. It has been shown that overall enzyme activity should be taken into consideration when determining the genesis of postoperative hyperenzymemia and diagnosing the topical (organic) damage. High lactate level (6-8 mmol/l) reflects profound circulatory hypoxia and shows a great likelihood of secondary damage of parenchymatous organs in patients after cardiopulmonary bypass surgery. Marked lactatacidosis combined with a 5-10-fold increase in enzyme activity in the early postoperative period is an unfavourable prognostic sign. Prolonged antagosan (trasilol) administration during cardiopulmonary bypass surgery may be one of the techniques preventing and correcting hypoxic organ damage.     

Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac intensive care

OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass. DESIGN: A prospective, observational, clinical study. SETTING: A tertiary pediatric cardiac center. PATIENTS: Eighty-two infants and children undergoing elective cardiac surgery between March and December 1999. MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis. CONCLUSIONS: Patients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.     

心外膜超声心动图在先天性心脏病矫治术中的作用

目的　探讨心外膜超声心动图 (IEE)在先天性心脏病矫治术中的作用。方法　对接受先天性心脏病矫治手术的患者分别在术中体外循环前、后作 IEE,证实或修正术前漏、误诊并即刻评价手术疗效。结果　共对 2 8例先心病手术矫治术患者作了 IEE检查 ,其中 2例患者在体外循环前新发现合并的畸型 ,纠正了 2例患者的术前诊断 ,在体外循环后及时发现 2例患者的手术并发症 ,此 6例患者的 IEE诊断均经手术证实。结论　 IEE能有效修正术前部分患者的漏、误诊 ,即刻评价手术疗效、发现围术期并发症 ,在先心病矫治术中有重要应用价值     

Cardiopulmonary bypass surgery in a patient with paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare acquired haemolytic anaemia. Cardiac bypass surgery in patients with PNH may be complicated by aggravation of haemolysis in addition to increased risk of infection, renal failure, bleeding and thrombosis. We describe a case of uncomplicated cardiopulmonary bypass surgery for aortic valve replacement and aortoplasty in a patient with PNH and discuss some recommendations to reduce the risk of peri-operative complications.     

Point-of-Care Testing of Hemostasis in Cardiac Surgery

An excessive perioperative blood loss, that requires transfusion of blood products, sometimes occurs in patients undergoing cardiopulmonary bypass for cardiac surgery. Blood loss and transfusion requirements in these patients may be reduced with a better control of heparin treatment and its reversal. Blood component administration in patients with excessive post-cardiopulmonary bypass bleeding has been empiric for a long time due to turnaround times of laboratory coagulation tests. Devices are now available for rapid, point-of-care assessment of hemostasis alterations to allow an appropriate, targeted therapy. In particular, a quick evaluation of platelet and coagulation defects with new point-of-care devices can optimize the administration of pharmacological and transfusion-based therapy in patients with excessive bleeding after cardiopulmonary bypass.     

体外循环手术患者血浆C3和C4的检测及临床意义

目的 了解体外循环手术(CPB)对患者血浆中补体C3、C4的影响.方法 用透射比浊法测定行心脏瓣膜置换术前后患者血浆中C3、C4的浓度,并进行比较.结果 术前与术后血浆中C3、C4差异有统计学意义,血浆中C3、C4降低的谷值在CPB末.结论 CPB导致术后早期大量补体激活,易引起全身性炎症反应综合征(SIRS),减少补体激活程度可降低炎症反应强度.     

To pump or not to pump?

Coronary artery bypass grafting is performed on the beating heart and thus requires the use of cardiopulmonary bypass. To avoid the complications associated with cardiopulmonary bypass, off-pump bypass (OPB) is viewed as a desirable alternative. Technological advancements have made OPB a viable option in an expanding population of patients. As a result, the number of OPB surgeries performed annually in the United States has increased. Critical care nurses are increasingly likely to provide care for patients after off-pump surgery. The differences between on-pump and OPB surgeries affect the postoperative nursing care requirements. While there are many common aspects of postoperative cardiac care for these 2 groups of surgical patients, there is a need to focus on the unique aspects of care for OPB patients. Despite promising short-term results in OPB patients, questions surrounding this procedure remain. Studies are under way to determine long-term graft patency.     

Copeptin as a marker of relative arginine vasopressin deficiency after pediatric cardiac surgery

Purpose

Relative arginine vasopressin (AVP) deficiency after pediatric cardiac surgery has recently been described. Copeptin, a more stable and easily measured product of pro-AVP processing, may be a means of identifying these patients. We aimed to determine if copeptin was correlated with AVP in these children and whether it can be a surrogate marker of relative AVP deficiency.

Methods

Patients <6?years of age with basic Aristotle scores ≥7 requiring surgery with cardiopulmonary bypass were prospectively enrolled. Plasma AVP and copeptin concentrations were measured pre-cardiopulmonary bypass and 4 and 24?h post-cardiopulmonary bypass. Relative AVP deficiency was defined a priori based on our previous work as AVP <9.2?pg/ml at 4?h post-cardiopulmonary bypass.

Results

Of 41 children enrolled, relative AVP deficiency was present in 13 (32?%). AVP and copeptin concentrations were significantly lower in these 13 children at 4?h post-cardiopulmonary bypass as compared to the other 28 patients. A significant positive association between plasma AVP and copeptin concentrations over time was determined. Based on log-transformed analyses, a 1?% increase in plasma AVP led to a 0.19?% increase in copeptin. Further, copeptin <1.12?ng/ml at 4?h post-cardiopulmonary bypass had a sensitivity of 92?% and a negative predictive value of 95?% for relative AVP deficiency.

Conclusions

Plasma AVP and copeptin are positively associated in children undergoing cardiac surgery. Copeptin may represent a useful means of identifying relative AVP deficiency in these patients.     

Single, percutaneous, femoral venous cannulation for cardiopulmonary bypass

Percutaneous femoral venous cannulation for cardiopulmonary bypass has emerged as an indispensable technique in the management of cardiac surgical procedures requiring cardiopulmonary bypass. A review of cases at Brigham and Women's Hospital (Boston, MA, USA) relying solely on percutaneous femoral venous cannulation for venous return to the heart-lung machine demonstrated achievable blood flow and complexity of case-load. Operations performed in this manner include, but are not limited to, coronary artery bypass grafting (CABG), valve, CABG/valve, and aortic procedures. Minimally invasive procedures and re-operations comprise a portion of each group. Complications of cardiopulmonary bypass and site-related complications were considered. Percutaneous femoral venous cannulation is a safe method to provide most patients with adequate venous return to perform any cardiac surgery. Patients demanding greater flow than this method will provide, may require a second venous cannula at some time during cardiopulmonary bypass.     

AANA journal course: update for nurse anesthetists--anesthetic considerations for minimally invasive direct vision coronary artery bypass grafting.

A recently developed procedure known as MIDCAB (minimally invasive direct vision coronary artery bypass) offers a select group of patients with coronary artery disease an alternative to coronary artery bypass grafting with cardiopulmonary bypass. Compared with customary coronary artery bypass graft surgery, the MIDCAB procedure has a smaller modified incision, requires less operative time, eliminates the risk of cardiopulmonary bypass, and is, as the name implies, far less invasive. Single or multiple vessels are revascularized while the heart remains warm and beating. Movement of the beating heart is dampened in the area of the targeted bypass vessel with the use of mechanical stabilizers by the surgeon. The heart rate may be pharmacologically slowed by the anesthetist. The combination of slowed heart rate and mechanical tamponade by the stabilizers may lead to profound hemodynamic and ischemic changes that may be poorly tolerated in a patient with multiple vessel disease and concurrent disease processes. Extubation and recovery times are far shorter for MIDCAB procedures, leading to earlier discharge and substantial cost savings. The surgical techniques for cardiac bypass surgery have evolved dramatically during the past few years. It is the unique combination of anesthetic monitoring, quick response to hemodynamic changes, and manipulation of physiologic parameters that makes providing anesthesia for minimally invasive cardiac bypass surgery exceptionally challenging.     

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.     

Activated coagulation time and the concentration of heparin in assessing the level of blood heparinization during operations using artificial blood circulation

Blood heparinization was assessed, using two techniques (activated coagulation time--ACT and heparin concentration) in 31 patients during cardiopulmonary bypass surgery. It has been shown that ACT-technique, not always revealing heparin concentration, may serve as a criterion for blood heparinization adequacy during cardiopulmonary bypass, as in every case it reflects individual changes in anticoagulant blood activity.     

Calpain inhibition decreases endothelin-1 levels and pulmonary hypertension after cardiopulmonary bypass with deep hypothermic circulatory arrest

OBJECTIVE: Cardiopulmonary bypass in infants and children can result in cardiopulmonary dysfunction through ischemia and reperfusion injury. Pulmonary hypertension and injury are particularly common and morbid complications of neonatal cardiac surgery. Inhibition of calpain, a cysteine protease, has been shown to inhibit reperfusion injury in adult organ systems. The hypothesis is that calpain inhibition can alleviate the cardiopulmonary dysfunction seen in immature animals following ischemia and reperfusion with cardiopulmonary bypass. DESIGN: Animal case study. SETTING: Medical laboratory. SUBJECTS: Crossbred piglets (5-7 kg). INTERVENTIONS: Piglets were cooled with cardiopulmonary bypass to 18 degrees C followed by deep hypothermic circulatory arrest for 120 mins. Animals were rewarmed to 38 degrees C on cardiopulmonary bypass and maintained for 120 mins. Six animals were administered calpain inhibitor (Z-Leu-Leu-Tyr-fluoromethyl ketone; 1 mg/kg, intravenously) 60 mins before cardiopulmonary bypass. Nine animals were administered saline as a control. Plasma endothelin-1, pulmonary and hemodynamic function, and markers of leukocyte activity and injury were measured. MEASUREMENTS AND MAIN RESULTS: Calpain inhibition prevented the increased pulmonary vascular resistance seen in control animals (95.7 +/- 39.4 vs. 325.3 +/- 83.6 dyne.sec/cm, respectively, 120 mins after cardiopulmonary bypass and deep hypothermic circulatory arrest, p = .05). The attenuation in pulmonary vascular resistance was associated with a blunted plasma endothelin-1 response (4.91 +/- 1.72 pg/mL with calpain inhibition vs. 10.66 +/- 6.21 pg/mL in controls, p < .05). Pulmonary function after cardiopulmonary bypass was better maintained after calpain inhibition compared with controls: Po2/Fio2 ratio (507.2 +/- 46.5 vs. 344.7 +/- 140.5, respectively, p < .05) and alveolar-arterial gradient (40.0 +/- 17.2 vs. 128.1 +/- 85.2 mm Hg, respectively, p < .05). Systemic oxygen delivery was higher after calpain inhibition compared with controls (759 +/- 171 vs. 277 +/- 46 mL/min, respectively, p < .001). In addition, endothelial nitric oxide synthase activity in lung tissue was maintained with calpain inhibition. CONCLUSIONS: The reduction in plasma endothelin-1 and maintenance of lung endothelial nitric oxide levels after cardiopulmonary bypass and deep hypothermic circulatory arrest with calpain inhibition were associated with reduced pulmonary vascular resistance. Improved gas exchange and higher systemic oxygen delivery suggest that calpain inhibition may be advantageous for reducing postoperative cardiopulmonary dysfunction commonly associated with pediatric heart surgery and cardiopulmonary bypass.     

Perioperative effects and safety of nesiritide following cardiac surgery in children

Nesiritide (Natrecor, Scios Inc), human B-type natriuretic peptide, has hemodynamic effects that may be beneficial in pediatric patients after cardiac surgery. Experience with nesiritide and pediatrics is limited. The purpose of this study was to evaluate perioperative effects and safety of nesiritide in pediatric cardiothoracic surgery. Seventeen patients with congenital heart disease undergoing cardiac surgery were given a loading dose (1 microg/kg) while on cardiopulmonary bypass (constant flow) followed by continuous infusion for 24 hours (0.01 microg/kg/min x 6 hours, then 0.02 microg/kg/min x 18 hours). A 7% decrease in mean blood pressure was seen following nesiritide loading dose on cardiopulmonary bypass. No patient required intervention for hypotension while receiving nesiritide load or infusion. Nesiritide load during surgery and continuous infusion after cardiac surgery in pediatric patients resulted in no significant hemodynamic compromise.     

CT血管造影分析体外循环与非体外循环冠状动脉旁路移植后的桥血管通畅率

背景:近年来,非体外循环冠状动脉旁路移植后桥血管通畅率是否与传统的体外循环冠状动脉旁路移植相同存在争议.目的:探讨体外循环与非体外循环冠状动脉旁路移植后桥血管时间通畅率的差异性.方法:选取同一操作者行体外循环冠状动脉旁路移植患者100例,按其临床特征及桥血管病变危险因素匹配抽取非体外循环冠状动脉旁路移植患者137例.采用64排多螺旋CT血管造影分析冠脉搭桥后1个月,1年,2年,3年,4年的桥血管通畅情况.结果与结论:共对641条桥血管进行评价,两组中左侧乳内动脉桥血管时间通畅率均高于大隐静脉桥,两组左侧乳内动脉桥和人隐静脉桥血管时间通畅率比较差异均无显著性意义.说明非体外循环与体外循环冠状动脉旁路移植后患者桥血管时间通畅率相似,对于某些适当的患者来说,非体外循环冠状动脉旁路移植不失为一个良好的选择.