Perioperative steroids administration in pediatric cardiac surgery: a meta-analysis of randomized controlled trials*.

OBJECTIVE: To evaluate the effects of prophylactic perioperative corticosteroid administration, compared with placebo, on postoperative mortality and clinical outcomes (renal dysfunction, duration of mechanical ventilation, and ICU length of stay) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. DATA SOURCES: MEDLINE and Cochrane Library were screened through August 2013 for randomized controlled trials in which perioperative steroid treatment was adopted. STUDY SELECTION: Included were randomized controlled trials conducted on pediatric population that reported clinical outcomes about mortality and morbidity. DATA EXTRACTION: Eighty citations (PubMed, 48 citations; Cochrane, 32 citations) were identified, of which 14 articles were analyzed in depth and six articles fulfilled eligibility criteria and reported mortality data (232 patients), two studies reported ICU length of stay and mechanical ventilation duration (60 patients), and two studies reported renal dysfunction (49 patients). DATA SYNTHESIS: A nonsignificant trend of reduced mortality was observed in steroid-treated patients (11 [4.7%] vs 4 [1.7%] patients; odds ratio, 0.41; 95% CI, 0.14-1.15; p = 0.089). Steroids had no effects on mechanical ventilation time (117.4 ± 95.9 hr vs 137.3 ± 102.4 hr; p = 0.43) and ICU length of stay (9.6 ± 4.6 d vs 9.9 ± 5.9 d; p = 0.8). Perioperative steroid administration reduced the prevalence of renal dysfunction (13 [54.2%] vs 2 [8%] patients; odds ratio, 0.07; 95% CI, 0.01-0.38; p = 0.002). CONCLUSION: Despite a demonstrated attenuation of cardiopulmonary bypass-induced inflammatory response by steroid administration, a systematic review of randomized controlled trials performed so far reveals that steroid administration has potential clinical advantages (lower mortality and significant reduction of renal function deterioration). A larger prospective randomized study is needed to verify clearly the effects of steroid prophylaxis in pediatric patients.

Anti-inflammatory strategies to reduce acute kidney injury in cardiac surgery patients: a meta-analysis of randomized controlled trials.

Acute kidney injury (AKI) after cardiac operations is a serious complication associated with postoperative mortality. Multiple factors contribute to AKI development, principally ischemia-reperfusion injury and inflammatory response. It is well proven that glucocorticoid administration, leukocyte filter application, and miniaturized extracorporeal circuits (MECC) modulate inflammatory response. We conducted a systematic review of randomized controlled trials (RCTs) in which one of these inflammatory system modulation strategies was used, with the aim to evaluate the effects on postoperative AKI. MEDLINE and Cochrane Library were screened through November 2011 for RCTs in which an inflammatory system modulation strategy was adopted. Included were trials that reported data about postoperative renal outcomes. Because AKI was defined by different criteria, including biochemical determinations, urine output, or dialysis requirement, we unified renal outcome as worsening renal function (WRF). We identified 14 trials for steroids administration (931 patients, WRF incidence [treatment vs. placebo]: 2.7% vs. 2.4%; OR: 1.13; 95% CI: 0.53-2.43; P = 0.79), 9 trials for MECC (947 patients, WRF incidence: 2.4% vs. 0.9%; OR: 0.47; 95% CI: 0.18-1.25; P = 0.13), 6 trials for leukocyte filters (374 patients, WRF incidence: 1.1% vs. 7.5%; OR: 0.18; 95% CI: 0.05-0.64; P = 0.008). Only leukocyte filters effectively reduced WRF incidence. Not all cardiopulmonary bypass-related anti-inflammatory strategies analyzed reduced renal damage after cardiac operations. In adult patients, probably other factors are predominant on inflammation in determining AKI, and only leukocyte filters were effective. Large multicenter RCTs are needed in order to better evaluate the role of inflammation in AKI development after cardiac operations.

Monitoring incomplete heparin reversal and heparin rebound after cardiac surgery.

OBJECTIVES: To assess the incidence of incomplete heparin reversal and heparin rebound after cardiac surgery with cardiopulmonary bypass (CPB) and the ability of the activated coagulation time (ACT) and thromboelastography (TEG) to detect these phenomena. DESIGN: Prospective single-center study. SETTING: University hospital. PARTICIPANTS: Forty-one patients undergoing elective cardiac surgery with CPB and with normal preoperative TEG parameters. INTERVENTIONS: ACT, TEG, and plasma heparin levels were measured in all patients at 5 different times between 20 minutes and 3 hours after protamine administration. The variability of TEG reaction time (R) with and without heparinase (delta-R [DR]) was used to detect the presence of residual heparin. MEASUREMENTS AND MAIN RESULTS: Plasma heparin expressed as anti-FXa activity was detected in 180 (88%) samples. At univariate analysis, ACT, R-kaolin (R-k), and DR significantly correlated with plasma heparin concentration (respectively, p = 0.007, p = 0.006, and p = 0.002). At multivariate analysis, R-k and DR remained associated with plasma heparin concentration (respectively, p = 0.014 and p = 0.004). Greater quartiles of heparin were associated with higher values of R-k and DR. Combined procedures had significantly lower DR than isolated procedures (p = 0.017), and CPB time and heparinization time positively correlated with R-k (respectively, p = 0.044 and p = 0.022). No association was observed between heparin concentration, ACT, and TEG parameters with postoperative bleeding and need for blood and blood components transfusions. CONCLUSIONS: Heparin rebound and incomplete heparin reversal are very common phenomena after cardiac surgery with CPB; ACT is not able to detect residual heparin activity, whereas TEG analysis with and without heparinase allows the diagnosis of heparin rebound.

Mid-term results of endoscopic mitral valve repair and insights in surgical techniques for isolated posterior prolapse.

BACKGROUND: The adoption of minimally invasive techniques to perform mitral valve repair surgery is increasing. This is enhanced by the compelling evidence of satisfactory short-term results and lower major morbidity. We analyzed mid-term follow-up results of our experience, and further compared two techniques: isolated leaflet resection and neochord implantation for posterior leaflet prolapse. METHODS: Data for all consecutive endoscopic mitral valve repairs via video-assisted right anterior mini-thoracotomy were analyzed between December 2012 and September 2021. The early and mid-term follow-up results were ascertained. The main outcome was the incidence of mortality and the recurrence of significant mitral regurgitation during follow-up which were summarized by the Kaplan-Meier estimator and compared between treatment arms using the stratified log-rank test. Secondary outcomes were the early-postoperative results including 30-days mortality and the occurrence of major complications. RESULTS: A total of 309 patients were included. Along with ring annuloplasty, 136 (44.4%) patients received posterior leaflet resection (122 isolated) whereas 97 (31.1%) underwent posterior leaflet chords implantation (88 isolated). Forty-nine patients had annuloplasty alone. In-hospital mortality was 1.0%. Mean follow-up was 28.8 ± 22.0 months (maximum 8.3 years). Kaplan-Meier survival rate at 5 years was 97.3 ± 1.0%, mitral regurgitation ([Formula: see text]3+) or valve reoperation free-survival at 5 years was estimated as 94.5 ± 2.3%. Subgroup time-to-event analysis for the indexed outcomes showed no statistical significance between the techniques. CONCLUSIONS: Endoscopic mitral valve repair is safe and associated with excellent short- and mid-term outcomes. No differences were found between leaflet resection and gore-tex chords implantation for posterior leaflet prolapse.

A biocompatible cardiopulmonary bypass strategy to reduce hemostatic and inflammatory alterations: a randomized controlled trial.

OBJECTIVE: Cardiopulmonary bypass (CPB) systems without a venous reservoir rarely are adopted clinically. The effects of a biocompatible CPB system with a venous reservoir were evaluated on the activation of the coagulation and inflammatory systems. DESIGN: A prospective, randomized controlled trial. SETTING: A university hospital (single center). PARTICIPANTS: Eighty-three coronary artery bypass graft (CABG) surgery patients were assigned to the Physio group (closed venous reservoir, phosphorylcholine coating, and no cardiotomy suction) or the Standard group (open, noncoated, and cardiotomy suction used). METHODS: Blood samples were obtained at 6 different time points before, during, and after surgery. Nuclear factor-kB (NF-κB) was evaluated before surgery and 2 and 24 hours after surgery. Myocardial damage was evaluated measuring cardiac troponin I. MEASUREMENTS AND MAIN RESULTS: Interleukin (IL)-6 (a marker of inflammation), prothrombin fragment 1-2 (PF-1.2, a marker of thrombin generation), plasmin-antiplasmin complex (PAP, a marker of fibrinolysis), and platelet factor 4 (PF4, a marker of platelet activation) were measured. The DNA binding activity of proinflammatory transcription factor NF-κB was quantified in the isolated lymphomonocyte cells. Surgery caused changes of all plasma biomarkers. This reaction was attenuated strongly in the Physio group; PF-1.2, PAP, and PF4 all were decreased significantly. In the Physio group, a significantly lower cardiac troponin I release was observed postoperatively. After surgery, NF-κB activity was reduced in the Physio group although this difference was not statistically significant. CONCLUSIONS: A multimodal strategy using a closed and phosphorylcholine-coated CPB circuit together with the avoidance of cardiotomy suction reduced activation of the coagulation and fibrinolytic systems intraoperatively, although these changes did not persist postoperatively. However, no difference in clinical outcome was appreciated on a larger scale.

Protective effects of steroids in cardiac surgery: a meta-analysis of randomized double-blind trials.

OBJECTIVE: Cardiac surgery and cardiopulmonary bypass (CPB) induce an acute inflammatory response contributing to postoperative morbidity. The use of steroids as anti-inflammatory agents in surgery using CPB has been tested in many trials and has been shown to have good anti-inflammatory effects but no clear clinical advantages for the lack of an adequately powered sample size. The aim of this study was to evaluate the effects of steroid treatment on mortality and morbidity after cardiac surgery. DESIGN: A systematic meta-analysis of randomized double-blind trials (RDBs). SETTING: A university hospital. PARTICIPANTS: Adult patients who underwent cardiac surgery. MEASUREMENTS AND MAIN RESULTS: A trial search was performed through PubMed and Cochrane databases from 1966 to January 2009. Among 104 clinical trials reviewed, 31 RDB trials (1,974 patients) were considered suitable to be analyzed. A quality assessment of the trials was performed using the Jadad score. The types of steroid used in these trials were methylprednisolone (51.4%), dexamethasone (34.3%), hydrocortisone (5.7%), prednisolone (2.9%), or a combination of methylprednisolone and dexamethasone (5.7%). Steroid prophylaxis provided a protective effect preventing postoperative atrial fibrillation (odds ratio = 0.56; confidence interval [CI] 0.44-0.72, p < 0.0001), reducing postoperative blood loss (mean difference = -204.2 mL; CI from -287.4 to -121 mL; p < 0.0001), and reducing intensive care unit (mean difference = -6.6 hours; CI from -10.5 to -2.7 hours, p = 0.0007) and overall hospital stay (mean difference = -0.8 days; CI from -1.4 to -0.2 days, p = 0.01). Steroid prophylaxis had no effect on postoperative mortality, mechanical ventilation duration, re-exploration for bleeding, and postoperative infection. CONCLUSIONS: A systematic review of RDB trials reveals that steroid prophylaxis may reduce morbidity after cardiac surgery and does not increase the risk of postoperative infections.

The Preoperative Inflammatory Status Affects the Clinical Outcome in Cardiac Surgery.

AIMS: There are many reasons for the increase in post-operative mortality and morbidity in patients undergoing surgery. In fact, an activated inflammatory state before cardiac surgery, can potentially worsen the patient's prognosis and the effects of this preoperative inflammatory state in the medium-term remains unknown. METHODS: There were 470 consecutive patients who underwent cardiac surgery, and were divided in three groups according to the median values of preoperative C-reactive protein (CRP) and fibrinogen (FBG): The first group was the low inflammatory status group (LIS) with 161 patients (CRP < 0.39 mg/dL and FBG < 366 mg/dL); the second was the medium inflammatory status group (MIS) with 150 patients (CRP < 0.39 mg/dL and FBG ≥ 366 mg/dL or CRP ≥ 0.39 mg/dL and FBG < 366 mg/dL,); and the third was the high inflammatory status group (HIS) with 159 patients (CRP ≥ 0.39 mg/dL and FBG ≥ 366 mg/dL,). RESULTS: The parameters to be considered for the patients before surgery were similar between the three groups except, however, for age, left ventricular ejection fraction (LVEF) and the presence of arterial hypertension. The operative mortality was not significantly different between the groups (LIS = 2.5%, MIS = 6%, HIS = 6.9%, p = 0.16) while mortality for sepsis was significantly different (LIS = 0%, MIS = 1.3%, HIS = 3.7%, p = 0.03). The infections were more frequent in the HIS group (p = 0.0002). The HIS group resulted in an independent risk factor for infections (relative risk (RR) = 3.1, confidence interval (CI) = 1.2-7.9, p = 0.02). During the 48-months follow-up, survival was lower for the HIS patients. This HIS group (RR = 2.39, CI = 1.03-5.53, p = 0.05) and LVEF (RR = 0.96, CI = 0.92-0.99, p = 0.04) resulted in independent risk factors for mortality during the follow-up. CONCLUSIONS: The patients undergoing cardiac surgery with a preoperative highly activated inflammatory status are at a higher risk of post-operative infections. Furthermore, during the intermediate follow-up, the preoperative highly activated inflammatory status and LVEF resulted in independent risk factors for mortality.

Trials Comparing Percutaneous And Surgical Myocardial Revascularization: A Review.

INTRODUCTION: Ischemic heart diseases are the major leading cause of death worldwide. Revascularization procedures dramatically reduced the overall risk for death related to acute coronary syndromes. Two kinds of myocardial revascularization can grossly be outlined: percutaneous coronary intervention (PCI) and surgical coronary artery bypass graft intervention (CABG). The net clinical benefit coming from these two kinds of procedures is still under debate. METHODS: We have traced the state-of-the-art background about myocardial revascularization procedures by comparing the most important trials dealing with the evaluation of percutaneous interventions versus a surgical approach to coronary artery diseases. RESULTS: Both PCI and CABG have become effective treatments for revascularization of patients suffering from advanced CAD. The advance in technology and procedural techniques made PCI an attractive and, to some extent, more reliable procedure in the context of CAD. However, there are still patients that cannot undergo PCI and have to be rather directed towards CABG. CONCLUSION: CABG still remains the best strategy for the treatment of multiple vessel CAD due to improved results in term of survival and freedom from reintervention. Anyway, a systematic, multidisciplinary approach to revascularization is the fundamental behaviour to be chased in order to effectively help the patients in overcoming its diseases. The creation of the "heart team" seems to be a good option for the correct treatment of patients suffering from stable and unstable CAD.

Minimally invasive heart valve surgery: influence on coagulation and inflammatory response.

OBJECTIVES: Minimally invasive valve surgery (MIVS) is associated with improved clinical outcome but longer cardiopulmonary bypass (CPB) time. The aim of the present study is to compare inflammatory and coagulation parameters in patients undergoing minimally invasive or standard valve surgery. METHODS: A prospective non-randomized study was performed enrolling 79 patients undergoing mitral (20 right mini-thoracotomy and 18 standard sternotomy) and aortic valve (20 mini-sternotomy and 21 standard sternotomy) procedures. Blood samples were collected perioperatively to measure prothrombin fragment 1.2 (PF1.2, thrombin generation), plasmin antiplasmin complex (PAP, fibrinolysis), interleukin-6 (IL-6, inflammation). Plasma free haemoglobin (f-Hb) was assessed to evaluate haemolysis. RESULTS: Patients in the minimally invasive group were younger and had less comorbidities CPB and cross-clamp times were comparable considering both aortic and mitral procedures, but longer in the mini-thoracotomy group. IL-6 and PAP were reduced in the minimally invasive group, particularly 2 h after CPB (respectively 102 ± 114 vs 34 ± 49 pg/ml, P < 0.001 and 2137 ± 1046 vs 1207 ± 675 ng/ml, P < 0.001), PF1.2 was also reduced during and after the operation (688 ± 514 vs 571 ± 470, P = 0.02; 1600 ± 1185 vs 1042 ± 548, P < 0.001; 1487 ± 676 vs 1042 ± 541). Despite the use of vacuum-assisted active venous drainage (VAVD) f-Hb was significantly reduced in the minimally invasive group. The other routine biomarkers such as C-reactive protein, fibrinogen and cTnI were also reduced in the minimally invasive group. CONCLUSIONS: In a selected cohort of patients MIVS is associated to reduced inflammatory reaction and coagulopathy, supporting the clinical evidence of reduced postoperative bleeding and lower transfusion rate. Our data offer further suggestion supporting the adoption of minimally invasive approaches.

Acute kidney injury in high-risk cardiac surgery patients: roles of inflammation and coagulation.

AIMS: Acute kidney injury (AKI) is a common complication following cardiac surgery. Cardiopulmonary bypass elicits coagulation and inflammation activation and oxidative stress, all involved in AKI but never simultaneously assessed. We aimed to evaluate relations between oxidative stress, inflammatory and coagulation systems activation and postoperative renal function in patients with normal preoperative renal function. METHODS: Forty-one high-risk patients (EuroSCORE >6 and preoperative haemoglobin <12 g/dl in women and <13 g/dl in men) were prospectively enrolled. Prothrombin fragment 1.2 (coagulation marker), interleukin-6 and interleukin-10 (pro/anti-inflammatory markers) and 8-oxo-2'-deoxyguanosine (oxidative stress marker) were evaluated until postoperative day 5. RESULTS: Patients were divided into two groups according to estimated glomerular filtration rate reduction observed postoperatively (reduction <25% in 26 patients: NO-AKI group; reduction >25% in 15 patients: AKI group). No differences were found for inflammatory markers. Oxidative stress slightly increased in the AKI group. Twenty-four hours after the operation prothrombin fragment 1.2 levels were significantly higher in the AKI group (506.6 ±â€Š548 vs. 999 ±â€Š704.1 pmol/l; P = 0.018), and they were independently associated with estimated glomerular filtration rate reduction, with an area under the receiving operating characteristic of 0.744. CONCLUSION: Thrombin generation is higher in patients with renal function worsening, and it is an independent risk factor for AKI in patients with anaemia, possibly leading to microcirculation impairment and tubular cells damage.

The Effects of Steroids on Coagulation Dysfunction Induced by Cardiopulmonary Bypass: A Steroids in Cardiac Surgery (SIRS) Trial Substudy.

Cardiopulmonary bypass (CPB) surgery, despite heparin administration, elicits activation of coagulation system resulting in coagulopathy. Anti-inflammatory effects of steroid treatment have been demonstrated, but its effects on coagulation system are unknown. The primary objective of this study is to assess the effects of methylprednisolone on coagulation function by evaluating thrombin generation, fibrinolysis, and platelet activation in high-risk patients undergoing cardiac surgery with CPB. The Steroids In caRdiac Surgery study is a double-blind, randomized, controlled trial performed on 7507 patients worldwide who were randomized to receive either intravenous methylprednisolone, 250 mg at anesthetic induction and 250 mg at initiation of CPB (n = 3755), or placebo (n = 3752). A substudy was conducted in 2 sites to collect blood samples perioperatively to measure prothrombin fragment 1.2 (PF1+2, thrombin generation), plasmin-antiplasmin complex (PAP, fibrinolysis), platelet factor 4 (PF4 platelet activation), and fibrinogen. Eighty-one patients were enrolled in the substudy (37 placebo vs 44 in treatment group). No difference in clinical outcome was detected, including postoperative bleeding and need for blood products transfusion. All patients showed changes of all plasma biomarkers with greater values than baseline in both groups. This reaction was attenuated significantly in the treatment group for PF1.2 (P = 0.040) and PAP (P = 0.042) values at the first intraoperative measurement. No difference between groups was detected for PF4. Methylprednisolone treatment attenuates activation of coagulation system in high-risk patients undergoing CPB surgery. Reduction of thrombin generation and fibrinolysis activation may lead to reduced blood loss after surgery.

Cardiac troponin I and creatine kinase-MB release after different cardiac surgeries.

AIMS: To conduct a comparative study of cardiac troponin I (cTnI) and MB isoenzyme of serum creatine kinase (CK-MB) after different cardiac surgeries. METHODS: Consecutive cardiac operations under cardiopulmonary bypass (200 adults, 144 men, 68 ±â€Š11 years): 67 coronary artery bypass graft (CABG), 27 aortic valve surgery, 21 mitral valve surgery, 11 thoracic aorta surgery, and 74 combined surgery. Postoperative cTnI and CK-MB were measured on admission to the ICU and at fixed time until the fifth postoperative day. RESULTS: Peak values of cTnI (median 5.8 ng/ml; interquartile range 3.6-11.9) and CK-MB (29.0 ng/ml; 15.6-60.4) were reached mainly within 18 h after the end of surgery (85% of cTnI and 95% of CK-MB highest determinations) without differences among groups. Cardiopulmonary bypass and cross-clamp time significantly correlated with markers' peak values. At multivariate analysis, mitral valve surgery showed greater cTnI, CK-MB, and their cumulative area under the curve than other isolated procedures. Thoracic aorta surgery showed lower cumulative area under the curve for both markers than CABG and combined surgery. Mitral valve surgery had significant later reduction of both markers in comparison with other procedures. No patient in mitral valve surgery group reached cTnI values in the normal laboratory range within 5 postoperative days. CONCLUSION: Release pattern of cTnI and CK-MB after heart surgery depends on the type of procedure. Mitral valve surgery was characterized by highest and longest elevation of postoperative markers' concentration. Determinants of differences in myocardial injury biomarkers and their prognostic value after valve surgery should be accurately assessed.

Antithrombin administration in patients with low antithrombin values after cardiac surgery: a randomized controlled trial.

BACKGROUND: Antithrombin (AT) concentrations are reduced after cardiac surgery with cardiopulmonary bypass compared with the preoperative levels. Low postoperative AT is associated with worse short- and mid-term clinical outcomes. The aim of the study is to evaluate the effects of AT administration on activation of the coagulation and fibrinolytic systems, platelet function, and the inflammatory response in patients with low postoperative AT levels. METHODS: Sixty patients with postoperative AT levels of less than 65% were randomly assigned to receive purified AT (5000 IU in three administrations) or placebo in the postoperative intensive care unit. Thirty patients with postoperative AT levels greater than 65% were observed as controls. Interleukin 6 (a marker of inflammation), prothrombin fragment 1-2 (a marker of thrombin generation), plasmin-antiplasmin complex (a marker of fibrinolysis), and platelet factor 4 (a marker of platelet activation) were measured at six different times. RESULTS: Compared with the no AT group and control patients, patients receiving AT showed significantly higher AT values until 48 hours after the last administration. Analysis of variance for repeated measures showed a significant effect of study treatment in reducing prothrombin fragment 1-2 (p=0.009; interaction with time sample, p=0.006) and plasmin-antiplasmin complex (p<0.001; interaction with time sample, p<0.001) values but not interleukin 6 (p=0.877; interaction with time sample, p=0.521) and platelet factor 4 (p=0.913; interaction with time sample, p=0.543). No difference in chest tube drainage, reopening for bleeding, and blood transfusion was observed. CONCLUSIONS: Antithrombin administration in patients with low AT activity after surgery with cardiopulmonary bypass reduces postoperative thrombin generation and fibrinolysis with no effects on platelet activation and inflammatory response.

Haemostasis alterations in coronary artery bypass grafting: comparison between the off-pump technique and a closed coated cardiopulmonary bypass system.

OBJECTIVES: To compare coagulation and fibrinolysis activation in off-pump coronary artery bypass operation and in patients in whom a closed phosphorylcholine-coated cardiopulmonary bypass system was applied. Cardiopulmonary bypass induces activation of coagulative and fibrinolytic systems, which together with intraoperative haemodilution augment the risk of postoperative bleeding and transfusion of blood products. METHODS: Thirty-six off-pump coronary artery bypass and 36 coronary artery bypass grafting patients in whom a closed, phosphorylcholine-coated cardiopulmonary bypass system with a closed-collapsible venous reservoir (Physio group) was used were prospectively enrolled. Activation of coagulation and fibrinolytic systems was assessed evaluating the release of prothrombin fragment 1.2 and plasmin-antiplasmin complex preoperatively (T0), 30 min after heparin administration (T1), 15 min after protamine administration (T2), 3 h after protamin administration (T3) and on postoperative days 1 (T4) and 5 (T5). Platelet function was evaluated through Platelet Function Analyzer 100(®). RESULTS: During the operation, prothrombin fragment 1.2 and plasmin-antiplasmin levels were slightly higher in the Physio group, the difference being not statistically significant. In the off-pump coronary artery bypass group, prothrombin fragment 1.2 was significantly higher at T3 (618.7 ± 282.7 vs 416.6 ± 250.2 pmol/l; P = 0.006), T4 (416.7 ± 278.8 vs 310.2 ± 394.6 pmol/l; P < 0.001) and T5 (629.3 ± 295.2 vs 408.4 ± 409.7 pmol/l; P = 0.002), and plasmin-antiplasmin was significantly higher at T4 (731.1 ± 790 vs 334 ± 300.8 ng/ml; P = 0.019) and T5 (1744.4 ± 820.7 vs 860.1 ± 488.4 ng/ml; P = 0.003). Platelet Function Analyzer 100® closure time values were significantly higher in the Physio group patients at T3 (131.3 ± 105.7 vs 215.6 ± 58.9 s; P = 0.002). The off-pump coronary artery bypass patients had greater chest tube drainage (874.3 ± 371.5 vs 629.1 ± 334.5 ml; P = 0.005). The mean priming volume was 1240 ± 215 ml in the Physio group. Much more Physio patients received red blood cell transfusions (14 vs 25 patient; P = 0.009), because of higher intraoperative transfusion rates (6 vs 15 patients; P = 0.016). Despite similar preoperative haemoglobin levels (13 ± 1.2 vs 12.6 ± 1.4 g/dl; P = 0.2), postoperative haemoglobin levels were significantly lower in the Physio group. CONCLUSIONS: The Physio cardiopulmonary bypass approach does not significantly alter haemostasis during the operation compared with off-pump coronary artery bypass providing a reduced activation in the postoperative period reducing also chest tube drainage. However, further priming volume reduction is required to decrease intraoperative red blood cell transfusion.

Activation of the receptor activator of the nuclear factor-κB ligand pathway during coronary bypass surgery: comparison between on- and off-pump coronary artery bypass surgery procedures.

OBJECTIVES: The receptor activator of the nuclear factor kappa-B (NF-κB) ligand (RANKL), its membrane receptor RANK and its decoy receptor osteoprotegerin (OPG) are all members of the tumour necrosis factor family involved in bone metabolism and immune response. We evaluated the activation of the OPG/RANKL/RANK pathway in patients undergoing cardiac surgery with and without cardiopulmonary bypass (CPB). METHODS: Twenty consecutive patients undergoing elective coronary artery surgery were enrolled in the study and assigned either to the on-pump or to the off-pump group. Pre- and postoperative serum levels of OPG and RANKL were evaluated by enzyme-linked immunosorbent assay; gene expression of OPG, RANKL, RANK and NF-κB p50 subunits were determined by real-time polymerase chain reaction in peripheral blood T-cells and monocytes. RESULTS: Serum levels of OPG significantly increased after surgery in both groups, whereas serum levels of RANKL did not differ over time. T-cells from the on-pump group showed increased gene expression of OPG, RANKL and RANK after the intervention, whereas no mRNA variation for these genes was detected in T-cells from off-pump patients. Gene expression of p50 subunit increased in T-cells and monocytes from both groups. CONCLUSIONS: Cardiac surgery induces the activation of the OPG/RANKL/RANK pathway; both on- and off-pump procedures are associated with increased postoperative OPG serum levels and up-regulation of the NF-κB p50 subunit.

Hemostasis alterations in patients with acute aortic dissection.

BACKGROUND: Surgery for acute aortic dissection (AAD) is frequently complicated by excessive postoperative bleeding and blood product transfusion. Blood flow through the nonendothelialized false lumen is a potential trigger for the activation of the hemostatic system; however, the physiopathology of the aortic dissection induced coagulopathy has never been precisely studied. The aim of the present study is the evaluation of the coagulation and fibrinolytic systems and platelet activation in patients undergoing surgery for AAD. METHODS: Eighteen patients undergoing emergent surgery for Stanford type A AAD were enrolled in the study. The activation of the coagulation and fibrinolytic systems and platelet activation were evaluated at 6 different time points before, during, and after the operation, measuring prothrombin fragment 1.2 (F1.2), plasmin-antiplasmin complex, and platelet factor 4, respectively. RESULTS: All measured biomarkers were increased before, during, and after the operations indicating a systemic activation of coagulation, fibrinolysis, and platelets. These changes were pronounced even preoperatively (T0), and soon after the beginning of cardiopulmonary bypass (T1) when the influence of hypothermia and prolonged cardiopulmonary bypass time were not yet involved. Time from symptom onset to intervention inversely correlated with preoperative F1.2 (r=-0.75; p=0.002) and plasmin-antiplasmin levels (r=-0.57; p=0.034). CONCLUSIONS: Blood flow through the false lumen is a powerful activator of the hemostatic system even before the operation. This remarkable activation may influence postoperative outcome of AAD patients.

D-dimers are not always elevated in patients with acute aortic dissection.

In patients with acute aortic dissection, an early diagnosis is essential to anticipate aortic rupture, cardiac tamponade, organ ischemia and improve surgical results. A specific blood laboratory marker able to rule out the presence of aortic dissection has not been identified yet. Recently, several studies suggested using D-dimers as a negative predicting test to rule out diagnosis of acute aortic dissection in patients presenting with chest pain. In 61 patients with confirmed aortic dissection, preoperative D-dimers were assayed and correlated with time from symptom onset and extension of the false lumen dissection (according with De Bakey classification). Abnormal D-dimers values were considered those being greater than 400 microg/l. D-dimers values were above 400 microg/l in 50 patients (82%) and below 400 microg/l in 11 patients (18%). There was no correlation between preoperative D-dimers values and time from symptoms onset (r = -0.232; P = 0.1). We found that D-dimers are not always elevated in patients presenting with acute aortic dissection. Given the potential devastating effects of denying the diagnosis of acute aortic dissection with consequent delay of adequate treatment, a word of caution regarding the negative predictive value of D-dimer test in the diagnosis of aortic dissection seems warranted.

Ochratoxin A inhibits the production of tissue factor and plasminogen activator inhibitor-2 by human blood mononuclear cells: another potential mechanism of immune-suppression.

The mycotoxin ochratoxin A (OTA), an ubiquitous contaminant of food products endowed with a wide spectrum of toxicity, affects several functions of mononuclear leukocytes. Monocytes/macrophages play a major role in fibrin accumulation associated with immune-inflammatory processes through the production of tissue factor (TF) and plasminogen activator inhibitor 2 (PAI-2). We studied the effect of OTA on TF and PAI-2 production by human blood mononuclear cells (MNC). The cells were incubated for 3 or 18 h at 37 degrees C with non toxic OTA concentrations in the absence and in the presence of lipopolysaccharide (LPS) or other inflammatory agents. TF activity was measured by a one-stage clotting test. Antigen assays were performed by specific ELISAs in cell extracts or conditioned media and specific mRNAs were assessed by RT-PCR. OTA had no direct effect on TF and PAI-2 production by MNC. However, OTA caused a dose-dependent reduction in LPS-induced TF (activity, antigen and mRNA) and PAI-2 (antigen and mRNA) production with >85% inhibition at 1 mug/ml. Similar results were obtained when monocyte-enriched preparations were used instead of MNC. TF production was also impaired by OTA (1 mug/ml) when MNC were stimulated with phorbol myristate acetate (98% inhibition), IL-1beta (83%) or TNF-alpha (62%). The inhibition of TF and PAI-2 induction might represent a hitherto unrecognized mechanism whereby OTA exerts immunosuppressant activity.