Procalcitonin nach extrakorporaler Zirkulation Synthese im Hepatosplanchnikusgebiet?

Procalcitonin (PCT) is an inflammatory peptide of still unknown origin. In this study we investigated a potential source for circulating PCT in patients undergoing coronary artery bypass grafting. METHODS: To determine PCT concentrations, arterial, liver-venous and mixed-venous blood samples were collected time matched perioperatively in 20 patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB). RESULTS: PCT concentrations significantly increased 4 hours postoperatively compared to baseline values (0.74 +/- 0.45 vs. 0.16 +/- 0.04 ng/ml). The highest concentrations were measured 18 hours postoperatively (1.44 +/- 1.01 ng/ml). PCT concentrations in liver venous samples were significantly higher (1.67 +/- 1.29 ng/ml) than in time matched collected arterial samples (1.44 +/- 1.01 ng/ml). CONCLUSION: These results provide evidence, that hepatosplanchnicus is a source for PCT synthesis in patients following CPB. The mechanism of PCT induction remains unclear. A loss of gut mucosal barrier function with translocation of endotoxins and the inflammatory response with release of cytokines following cardiopulmonary bypass has to be discussed.     

High-dose aprotinin reduces activation of hemostasis,allogeneic blood requirement,and duration of postoperative ventilation in pediatric cardiac surgery

BACKGROUND: Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial. METHODS: In a double-blind, randomized, and placebo-controlled study, the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 x 10(4) KIU/kg plus a bolus of 5 x 10(5) KIU (not weight adjusted) added to the pump prime. RESULTS: Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 +/- 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 +/- 2.9 nmol/L vs 14.5 +/- 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 +/- 0.6 ng/mL vs 2.3 +/- 3.1 ng/mL; p < 0.05), inflammatory markers (interleukin [IL]-6, IL-8, IL-10) increased over time without significant differences between the groups, and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group. Chest tube drainage was significantly reduced (24 hours: median 13.5 [IQR 12.2] mL/kg vs 19.4 [8.2] mL/kg; p < 0.05). All patients received one unit of packed cells to prime the heart lung machine. A second unit was needed significantly less often in the aprotinin group (13% vs 47%; p < 0.05). Postoperative oxygenation (pO2/FIO2 172 [IQR 128] mm Hg vs 127 [74]; p < 0.05) improved, and the time on ventilator was shorter in the aprotinin group (median 45 hours [IQR 94] vs 101 [IQR 74]; p < 0.05). No side effects were attributable to the use of aprotinin. CONCLUSIONS: High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the aprotinin group.     

Effect of induction therapy on kinetic of procalcitonin following uncomplicated heart transplantation

BACKGROUND: The aim of the study was to determine the early postoperative kinetics of serum procalcitonin (PCT) levels in uncomplicated heart transplant patients under induction therapy using antithymocyte globulin (ATG). METHODS: PCT serum concentrations were measured for 7 days in 30 adult patients (26 males, 4 females, mean age 54.5 +/- 7.7 years) undergoing uncomplicated orthotopic heart transplantation. Of the 30 patients, 28 received ATG and 2 with the same immunosuppression regimen had no induction therapy. The induction therapy consisted of 100 mg/day ATG and was started 6 hours postoperatively. RESULTS: Mean PCT levels immediately before HTX were <0.3 ng/mL in both groups. After the first ATG infusion patients developed a significant (p < 0.05) elevation in PCT plasma levels without any incidence of infectious disease with peak levels up to 11.7 +/- 19.7 ng/mL on postoperative day (POD) 1. Thereafter values continuously decreased independently of further ATG administration in all patients (6.7 +/- 10.5 ng/mL on POD 3, 3.2 +/- 7.4 ng/mL on POD 5 and 1.2 +/- 3.0 ng/mL on POD 7). In the non-ATG group a mild postoperative rise in the serum PCT was observed. The values peaked on POD 2 with 2.0 +/- 1.6 ng/mL and normalized within four days. CONCLUSIONS: Perioperative administration of ATG is associated with significantly increased PCT levels even in uncomplicated heart transplant recipients. This phenomenon should not be misinterpreted as systemic infection, as systemic inflammatory reaction that seems to be induced by ATG therapy is responsible for increased PCT production.     

Effect of cardiopulmonary bypass on serum procalcitonin and C-reactive protein concentrations

We have measured serum procalcitonin (PCT) concentrations after cardiac surgery in 36 patients allocated to one of three groups: group 1, coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) (n = 12); group 2, CABG without CPB (n = 12); and group 3, valvular surgery with CPB (n = 12). Serum PCT and C-reactive protein (CRP) concentrations were measured before operation, at the end of surgery and daily until postoperative day 8. Serum PCT concentrations increased, irrespective of the type of cardiac surgery, with maximum concentrations on day 1: mean 1.3 (SD 1.8), 1.1 (1.2) and 1.4 (1.2) ng ml-1 in groups 1, 2 and 3, respectively (ns). Serum PCT concentrations remained less than 5 ng ml-1 in all patients. Concentrations returned to normal by day 5 in all groups. To determine the effect of the systemic inflammatory response (SIRS) on serum PCT concentrations, patients were divided post hoc, without considering the type of cardiac surgery, into patients with SIRS (n = 19) and those without SIRS (n = 17). The increase in serum PCT was significantly greater in SIRS (peak PCT 1.79 (1.64) ng ml-1 vs 0.34 (0.32) ng ml-1 in patients without SIRS) (P = 0.005). Samples for PCT and CRP measurements were obtained from 10 other patients with postoperative complications (circulatory failure n = 7; active endocarditis n = 2; septic shock n = 1). In these patients, serum PCT concentrations ranged from 6.2 to 230 ng ml-1. Serum CRP concentrations increased in all patients, with no differences between groups. The postoperative increase in CRP lasted longer than that of PCT. We conclude that SIRS induced by cardiac surgery, with and without CPB, influenced serum PCT concentrations with a moderate and transient postoperative peak on the first day after operation. A postoperative serum PCT concentration of more than 5 ng ml-1 is highly suggestive of a postoperative complication.      

Effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass

BACKGROUND: We performed this prospective randomized study to determine the effect of a human urinary protease inhibitor (Ulinastatin) on respiratory function in pediatric patients undergoing cardiopulmonary bypass. METHODS: Twenty-two children were included in this study. They were randomly allocated to 1 of the following groups; a control group (n=11) or a Ulinastatin group (n=11) in which patients received 5000 U/kg of Ulinastatin. Arterial blood samples were obtained before cardiopulmonary bypass (CPB), immediately after CPB, and 30 min after protamine administration, as well as 3 hours after and 18 hours after CPB, and Interleukin-8 and neutrophil elastase concentration were evaluated. RESULTS: CPB time and aortic clamp time did not differ between the groups. Interleukin 8 and neutrophil elastase concentrations before CPB increased significantly immediately after CPB, these concentrations did not differ between the groups. However, neutrophil elastase concentrations of a Ulinastatin group were significantly lower than that of a control group at 30 min after protamine administration (a Ulinastatin group: 1011.3+/-539.1 mg/ml, a control group: 1619.7+/-595.7 mg/ml, p<0.05) and A-aDO2 of a Ulinastatin group was significantly lower than that of a control group at 2 hours after CPB (a Ulinastatin group: 67.1+/-70.6 mmHg, a control group: 169.2+/-116.3 g, p<0.05). CONCLUSIONS: These results suggest that Ulinastatin suppresses the increase in neutrophil elastase and protects the respiratory function in pediatric patients undergoing cardiopulmonary bypass.     

Interleukin-8 serum levels in patients with various types of open heart surgical procedures performed under extracorporeal circulation

Serum concentrations of proinflammatory cytokine interleukin-8 (IL-8) in 15 patients with surgically revascularized myocardium by triple venous cardiopulmonary bypass (CPB x 3) and in 10 patients with implanted artificial aortic valves (AV) were measured. Average IL-8 concentrations in (CPB x 3) patients and in those with artificial aortic valve were 7.3 +/- 11.6 pg/mL 24 hours before surgery, i.e. 3.3 +/- 3.4 pg/mL; six hours after surgical procedure 32.7 +/- 71.4 pg/mL, i.e. 8.9 +/- 9.9 pg/mL; and 24 hours after surgery 10.9 +/- 9.7 pg/mL, i.e. 8.3 +/- 4.6 pg/mL. Extracorporeal circulation (ECC) caused significant increase of IL-8 serum concentration in both investigated groups six hours after surgery. Comparing preoperative values of the both groups, as well as those of 6 and 24 hours after surgery, no significant values of IL-8 were found. Various types of open heart surgical procedures had no influence on the extent of the production and secretion of proinflammatory IL-8 cytokine measured in patients during 24 hours after surgery.     

C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery

BACKGROUND: It has been recognized that neurocognitive decline (NCD) often occurs as a complication in cardiac surgery. The early inflammatory response and C-reactive protein (CRP) was examined in relation to NCD and to a marker of axonal central nervous system (CNS) injury after cardiopulmonary bypass. METHODS: A cohort of patients undergoing coronary artery bypass grafting and/or valve procedures using cardiopulmonary bypass were administered a neurocognitive battery preoperatively and postoperatively at 6 hours and day 4. CRP, interleukin 1 beta, and interleukin 10 were quantified from serum. Increase of serum tau protein after surgery was used as a marker of axonal CNS damage. RESULTS: The rate of NCD was found to be 40.5% in this group. Surprisingly, known predictors of NCD did not differ significantly between patients with/without NCD. Patients with NCD had an early increase of CRP of a significantly higher magnitude than those without NCD (38.01 +/- 11.4 vs 16.49 +/- 3.5 mg/L, P = .042), interleukin 1ss (2.35 +/- 0.3 vs 1.20 +/- 0.2 pg/mL, P = .002), and interleukin 10 (29.77 +/- 4.7 vs 12.94 +/- 2.2 pg/mL, P < .001). Increase in serum Tau protein was significantly correlated to NCD (r = 0.50, P = .02). CONCLUSION: Perioperative increases in CRP and inflammatory cytokines are associated with NCD in patients after cardiopulmonary bypass. Thus, it appears that inflammation plays a key role in NCD pathophysiology, likely via axonal CNS injury, and could become a target for prevention.     

Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pediatric patients undergoing cardiac surgery: Part I.

Changes induced by cardiopulmonary bypass (CPB) may markedly affect the pharmacokinetics of drugs. Therefore, the pharmacokinetics of alfentanil before and after CPB were compared in infants and children undergoing cardiac surgery, who had been anesthetized with nitrous oxide in oxygen and low inspiratory concentrations of halothane. Six infants and six children were investigated. Before CPB, alfentanil, 200 micrograms/kg, and after CPB, alfentanil, 80 micrograms/kg, was infused in 10 minutes. Arterial blood samples were obtained before and after CPB for determination of plasma alfentanil concentrations. Bi-exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. A correction was made to account for the contribution of the first infusion to the plasma concentrations measured during and after the second infusion. Total sampling time before CPB (45 to 75 minutes) was too short to allow full characterization of the pharmacokinetics of alfentanil, but allowed estimation of the initial volume of distribution. The initial volume of distribution before CPB was smaller (68 +/- 37 mL/kg in infants and 80 +/- 32 mL/kg in children) than after CPB (235 +/- 58 mL/kg in infants and 179 +/- 99 mL/kg in children; P less than 0.001). The normalized area under the plasma concentration-time curve from 0 to 45 minutes was larger before CPB (17.9 +/- 2.9 mg.min/L in infants and 18.3 +/- 5.4 mg.min/L in children) than after CPB (11.1 +/- 2.9 mg.min/L in infants and 12.9 +/- 3.4 mg.min/L in children; P less than 0.001). Despite intravenous administration of atropine, arterial blood pressure and heart rate decreased significantly after alfentanil was given.     

Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ injury after cardiopulmonary bypass (CPB). Elderly patients appear to be especially prone to develop general inflammation. Use of pentoxifylline (PTX) before surgery may be a promising approach to minimize the negative effects of CPB in these patients. METHODS: In a prospective, randomized study, patients more than 80 years old undergoing aortocoronary artery bypass grafting received either PTX (n = 15) after induction of anesthesia (initial bolus of 300 mg followed by a continuous infusion of 1.5 mg.kg(-1).h(-1) during the next 2 days) or saline as placebo (control group; n = 15). Polymorphonuclear neutrophil (PMN) elastase, C-reactive protein (CRP), and interleukins (IL-6, IL-8, IL-10) were measured from arterial blood samples before surgery (T0), at the end of surgery (T1), 5 hours after surgery (T2), and at the morning of the first (T3) and second (T4) postoperative day. RESULTS: Postoperatively, PTX-treated patients less often needed catecholamines and were extubated earlier than the control patients (p < 0.05). On the intensive care unit, cardiac index inceased more in the PTX-treated (from 1.95 +/- 0.3 to 3.26 +/- 0.4 L.min(-1).m(-2)) than in the control patients (from 1.89 +/- 0.2 to 2.78 +/- 0.3 L.min(-1).m(-2)). Increase in CRP and PMN-elastase was significantly higher in the untreated control than in the PTX patients. After CPB, IL-6, IL-8, and IL-10 increased in both groups showing a significantly higher increase in the untreated control patients (IL-8 control: from 11.3 +/- 2.6 to 154.4 +/- 57 pg/mL [T1]); IL-8 PTX: from 10.9 +/- 2.7 to 71.8 +/- 23 pg/mL [T1]). CONCLUSIONS: In elderly cardiac surgery patients, use of PTX before surgery and continued after CPB resulted in less inflammatory response than in an untreated control group. The value of attenuating the inflammatory process by PTX on outcome in this patient population needs to be evaluated in further controlled studies.     

Disturbances in hepatocellular function during cardiopulmonary bypass using propofol anaesthesia.

BACKGROUND AND OBJECTIVE: Serum hyaluronate is thought to be an indicator of derangement in hepatocellular integrity, and the change in serum hyaluronate is a useful indicator in various liver disorders. We assessed the changes in serum hyaluronate in patients undergoing coronary artery bypass graft surgery. METHODS: Eleven patients scheduled for elective coronary artery bypass graft surgery were studied. An oximetry oxygen saturation catheter was inserted into the right hepatic vein to permit monitoring of hepatic venous oxygen saturation. Perioperative measurements included: haemodynamic variables; systemic oxygen delivery and uptake; arterial, mixed venous and hepatic venous oxygen saturation; arterial and hepatic venous plasma concentrations of lactate, arterial ketone body ratio (ratio of acetoacetate to 3-hydroxybutyrate); and arterial and hepatic venous hyaluronate were measured. RESULTS: Arterial and hepatic venous hyaluronate increased during cardiopulmonary bypass compared with the prebypass period. These increases returned to prebypass values after the cessation of bypass (hepatic venous hyaluronate value at the prebypass period: 26 +/- 13 ng mL(-1), during bypass: 77 +/- 40 ng mL(-1); 1 h after bypass: 57 +/- 42 ng mL(-1); 6 h after bypass: 32 +/- 15 ng L(-1), 24 h after bypass; 62 +/- 21 ng mL(-1); mean +/- SD, P < 0.05). The arterial and hepatic venous hyaluronate during cardiopulmonary bypass was correlated with total bilirubin and hepatic venous lactate concentrations 6 h after bypass (arterial hyaluronate at cardiopulmonary bypass period vs. total bilirubin at 6 h after bypass; r=0.793, P=0.0036, hepatic venous hyaluronate during bypass vs. that at 6 h after bypass; r=0.795, P=0.0035). CONCLUSIONS: Hepatocellular integrity might be disturbed during cardiopulmonary bypass when propofol anaesthesia is used.     

Tumor necrosis factor and clinical and metabolic courses after cardiac surgery in children

OBJECTIVE: This study was undertaken to determine the relationship between plasma tumor necrosis factor concentrations and hemodynamic and metabolic parameters during the postoperative clinical course in children undergoing cardiac surgery. METHODS: Tumor necrosis factor levels of 10 consecutive children undergoing surgery for repair of congenital heart defects were analyzed in blood samples drawn at predetermined time points during surgery and up to 24 hours thereafter. Clinical data were collected at these times for correlation to tumor necrosis factor levels. RESULTS: All the patients survived. Tumor necrosis factor was detected in all 10 children. Tumor necrosis factor levels declined after induction of general anesthesia (201 +/- 65 pg/mL) steadily decreasing during surgery, reaching 80 +/- 50 pg/mL at 24 hours after the operation. Tumor necrosis factor levels were found to be inversely correlated with mean blood pressure values and indicators of acidosis (bicarbonate levels and base excess, P <.03). They were not correlated with the durations of cardiopulmonary bypass and aortic crossclamping. CONCLUSIONS: Tumor necrosis factor released into the circulation during and after pediatric cardiac surgery under cardiopulmonary bypass may be related to the hemodynamic and acid-base changes observed after cardiac surgery. Elucidation of the relationship between tumor necrosis factor and patient outcome in high-risk patients awaits further studies.     

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.     

Strict thermoregulation attenuates myocardial injury during coronary artery bypass graft surgery as reflected by reduced levels of cardiac-specific troponin I

We assessed the cardioprotective effects of perioperative maintenance of normothermia by determining the perioperative profile of troponin I, a highly cardiac-specific protein important in risk stratification of patients with acute ischemic events. Candidates for their primary coronary artery bypass grafting (CABG) were randomized into a new thermoregulation system group, Allon( thermoregulation (AT; n = 30), and a routine thermal care (RTC; n = 30) group. Anesthetic and operative techniques were similar in both groups. Intraoperative warming was applied before and after cardiopulmonary bypass (CPB) and up to 4 h after surgery. Perioperative temperature and hemodynamic data were recorded. Blood samples for creatine kinase (CK) and its isoform, MB (CK-MB), and for cardiac-specific troponin I (cTnI) were obtained at predetermined intervals throughout the entire operation. Core and skin temperatures were higher in the AT group at all time points. The systemic vascular resistance was lower and the cardiac index higher in the AT group at all intra- and postoperative time points. Increases in CK, CK-MB, and cTnI levels indicated intraoperative ischemic insult in all patients. The respective CK levels for the AT and RTC groups were 53.3 +/- 22.7 IU/L and 47.9 +/- 17.86 IU/L at the time of anesthesia and 64.7 +/- 45.6 IU/L and 47.8 +/- 19.4 IU/L 30 min after the onset of surgery, demonstrating thereafter a steep increase before the discontinuation of CPB. CK-MB mass concentrations in both groups behaved almost identically. Pre-CPB cTnI levels at anesthesia induction were 0.3 +/- 0 ng/mL in both groups, followed by a distinctive profile observed after separation from CPB: 28.1 +/- 11.4 ng/mL, 26.05 +/- 9.20 ng/mL, and 22.3 +/- 8.9 ng/mL at discontinuation from CPB, chest closure, and 2 h after surgery, respectively, in the RTC group, versus 0.6 +/- 4.6 ng/mL, 6.6 +/- 5.5 ng/mL, and 7.9 +/- 4.76 ng/mL at these three time points, respectively, in the AT group (P < 0.01 between groups at the specified time points). Contrary to conventional thinking about the benefits of hypothermia, maintenance of normothermia throughout the non-CPB phases during CABG was demonstrated to be important in attenuating myocardial ischemic injury. Insofar as troponin I was more sensitive than other tested markers, it may provide important data on possible protection from myocardial insult and on other cardioprotective measures.     

Serum cardiac troponin-I elevation in neonatal cardiac surgery is lesion-dependent

OBJECTIVE: Serum cardiac troponin-I (cTn-I) is a marker for myocardial injury in adults that undergoes developmental isoform change. To determine its utility as a myocardial injury marker in neonates, the authors examined the perioperative pattern of cTn-I elevation in neonates undergoing surgical repair for hypoplastic left-heart syndrome (HLHS) and transposition of great arteries (TGA). DESIGN: A prospective cohort study. SETTING: The study was performed in a tertiary teaching hospital that is a major referral center for congenital cardiac surgery. PATIENTS: Forty-five neonates were enrolled, 17 with HLHS, 15 with TGA with intact septum (TGA + IVS), 8 with TGA with ventricular septal defect (TGA + VSD), and 5 neonates undergoing extracardiac surgery who did not require cardiopulmonary bypass (CPB). INTERVENTIONS: None. RESULTS: Preoperative cTn-I was elevated in all neonates undergoing cardiac surgery with CPB. Increases in postoperative cTn-I correlated with duration of aortic cross-clamp application and CPB. Peak elevation in serum cTn-I occurred between 6 and 24 hours postoperatively in all neonates after cardiac surgery. The perioperative pattern of cTn-I was different in TGA + VSD (peak cTn-I = 10.9 +/- 5.9 ng/mL) compared with HLHS (peak cTn-I = 4.62 +/- 3.4 ng/mL) and TGA + IVS (peak cTn-I = 4.46 +/- 3.5 ng/mL). CONCLUSION: It was found that perioperative elevations in serum cTn-I in neonates with TGA and HLHS were influenced by duration of aortic cross-clamp application, CPB, and the presence of VSD.     

The efficacy of low prime volume completely closed cardiopulmonary bypass in coronary artery revascularization.

PURPOSE: This study was conducted to evaluate and demonstrate the efficacy of low prime volume completely closed cardiopulmonary bypass (LPVP) in arrested coronary artery bypass grafting (CABG). We improved the percutaneous cardiopulmonary support (PCPS) circuit to reduce the deleterious effects of cardiopulmonary bypass (CPB). METHODS: Between April 1999 and May 2003, among 228 isolated CABG procedures, 47 procedures using LPVP (group L) and 86 procedures using standard prime volume open CPB (group S) were compared. The LPVP priming volume was 590 mL; the circuit was completely closed with a soft reservoir. Cardiac arrest was obtained by warm blood cardioplegia. RESULTS: The following average values were obtained: packed red blood cell transfusions, 0.88 +/- 1.4 U (group L) vs. 2.1 +/- 2.5 U (group S); intraoperative lowest hematocrit value, 28.7 +/- 4.6% (group L) vs. 22.4 +/- 3.3% (group S); blood loss over first 24 hours, 439 +/- 242 mL (group L) vs. 599 +/- 409 mL (group S); ventilation time, 5.1 +/- 3.1 hours (group L) vs. 10.4 +/- 14.9 hours (group S). CONCLUSION: Compared to standard prime volume open CPB, LPVP resulted in fewer deleterious operative effects. Less blood loss, fewer blood transfusions, and earlier patient recovery was noted with LPVP. Thus, LPVP is a very efficient form of CPB.     

Hydroxyethyl starch as a priming solution for cardiopulmonary bypass impairs hemostasis after cardiac surgery

We investigated the influence of hydroxyethyl starch (HES) as a priming solution for the cardiopulmonary bypass (CPB) circuit on postoperative hemostasis in 45 patients undergoing elective coronary artery bypass grafting. In a randomized sequence, 20 mL/kg of low-molecular-weight HES (HES 120; molecular weight 120,000 daltons), high-molecular-weight HES (HES 400; molecular weight 400,000 daltons), or 4% human albumin (ALB) was used as the main component of the CPB priming solution. The thromboelastographic values indicating the speed of solid clot formation (alpha-angle) and the strength of the fibrin clot (maximum amplitude and shear elastic modulus) were decreased up to 2 h after CPB in both HES groups. Four hours after the operation, blood loss through the chest tubes had increased in the HES groups: HES 120, mean 804 mL (range, 330-1390 mL); HES 400, mean 1008 mL (range, 505-1955 mL); and ALB, mean 681 mL (range, 295-1500 mL) (P < 0.05 between the HES 400 and ALB groups). We conclude that HES solutions, when given in doses of 20 mL/kg in connection with the CPB prime, compromise hemostasis after cardiac surgery. This effect appears related to formation of a less stable thrombus compared with that formed in the presence of ALB. IMPLICATIONS: The influence of hydroxyethyl starch (HES) on postoperative hemostasis was investigated in cardiac surgery. The thromboelastographic values indicated that HES solutions, when given in connection with the cardiopulmonary bypass prime, compromise hemostasis after cardiac surgery. This effect seems to occur through the formation of a less stable clot.     

Prostaglandin el attenuates impairment of cellular immunity after cardiopulmonary bypass

OBJECTIVE: It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS: Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity. RESULTS: PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%, control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1. CONCLUSION: PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs.     

The relationship between hirudin and activated clotting time: implications for patients with heparin-induced thrombocytopenia undergoing cardiac surgery.

Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r(2) = 0.83) linear relationships between ACT values and r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4 microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 microg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB. Implications: A modified activated clotting time test system that may be helpful in monitoring hirudin anticoagulation in patients with heparin-induced thrombocytopenia during cardiac surgery with cardiopulmonary bypass is described.     

Plasma tranexamic acid concentrations during cardiopulmonary bypass

Although tranexamic acid is used to reduce bleeding after cardiac surgery, there is large variation in the recommended dose, and few studies of plasma concentrations of the drug during cardiopulmonary bypass (CPB) have been performed. The plasma tranexamic acid concentration reported to inhibit fibrinolysis in vitro is 10 microg/mL. Twenty-one patients received an initial dose of 10 mg/kg given over 20 min followed by an infusion of 1 mg. kg(-1). h(-1) via a central venous catheter. Two patients were removed from the study secondary to protocol violation. Perioperative plasma tranexamic acid concentrations were measured with high-performance liquid chromatography. Plasma tranexamic acid concentrations (microg/mL; mean +/- SD [95% confidence interval]) were 37.4 +/- 16.9 (45.5, 29.3) after bolus, 27.6 +/- 7.9 (31.4, 23.8) after 5 min on CPB, 31.4 +/- 12.1 (37.2, 25.6) after 30 min on CPB, 29.2 +/- 9.0 (34.6, 23.8) after 60 min on CPB, 25.6 +/- 18.6 (35.1, 16.1) at discontinuation of tranexamic acid infusion, and 17.7 +/- 13.1 (24.1, 11.1) 1 h after discontinuation of tranexamic acid infusion. Four patients with renal insufficiency had increased concentrations of tranexamic acid at discontinuation of the drug. Repeated-measures analysis revealed a significant main effect of abnormal creatinine concentration (P = 0.02) and time (P < 0.001) on plasma tranexamic acid concentration and a significant time x creatinine concentration interaction (P < 0.001). IMPLICATIONS: A 10 mg/kg initial dose of tranexamic acid followed by an infusion of 1 mg.kg(-1).h(-1)produced plasma concentrations throughout the cardiopulmonary bypass period sufficient to inhibit fibrinolysis in vitro. The dosing of tranexamic acid may require adjustment for renal insufficiency.     

Perfusing and ventilating the patient's lungs during bypass ameliorates the increase in extravascular thermal volume after coronary bypass grafting

BACKGROUND: To test the hypothesis that bilateral extracorporeal circulation (ECC) (Drew technique) ameliorates the increase in extravascular thermal volume (ETV) observed after conventional cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting. METHODS: Thirty-four consecutive patients underwent either bilateral ECC (n = 24, additional cannulation of pulmonary artery and left atrium and lungs perfused and ventilated during bypass) or conventional CPB (n = 10, right atrial and aortic cannulation, lungs statically inflated to 4 mbar (0.41 cm H(2)O) with oxygen, 500 mL/min). Determinations of ETV (thermodye dilution technique) and intraoperative fluid balance were made before surgery, at the end of surgery, and 4 hours thereafter. In addition, interleukin (IL)-8, thromboxane B2 (TxB(2)), and endothelin (ET)-1 concentrations were measured in the right atrium and pulmonary vein at specified time points. RESULTS: Comparisons of ETV made at the start of surgery, after aortic declamping, and after termination of ECC, respectively, revealed an increase from 4.8 +/- 0.2 mL/kg (mean +/- SEM) to 6.7 +/- 0.4 mL/kg, and 6.3 +/- 0.3 mL/kg with conventional CPB but ETV remained unchanged at 5.2 +/- 0.3 mL/kg, 5.1 +/- 0.2 mL/kg, and 4.9 +/- 0.3 mL/kg with bilateral ECC. Priming volume (1,580 +/- 10 mL versus 2,213 +/- 77 mL, p < 0.001) and intraoperative fluid balance (+1,955 +/- 233 mL versus +2,654 +/- 210 mL, p < 0.05) were less with conventional CPB. Concentrations of IL-8, TxB(2), and ET-1 were not different between groups. CONCLUSIONS: Despite a significantly greater prime volume and a more positive intraoperative fluid balance, ETV did not change with bilateral ECC but increased with conventional CPB. Thus, using the patient's lungs as an oxygenator during bypass mitigates the increase in extravascular pulmonary fluid.