Giuseppe Scrascia

Is unilateral antegrade cerebral perfusion equivalent to bilateral cerebral perfusion for patients undergoing aortic arch surgery

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether unilateral antegrade cerebral perfusion is equivalent to bilateral cerebral plegia for cerebral protection during aortic arch surgery. Altogether 233 papers were found using the reported search, of which 17 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. These papers documented antegrade selective cerebral perfusion in a total of 3548 patients: bilateral cerebral perfusion in 2949 patients and unilateral perfusion in 599 patients. Both methods of cerebral perfusion resulted in neurological injury rates of <5%, but the period of antegrade cerebral perfusion allowed by bilateral perfusion was significantly higher. While unilateral perfusion allowed around 30-50 min, bilateral perfusion allowed 86 to over 164 min of ASCP with an acceptably low CVA rate. Therefore, we conclude that while both methods are acceptable, once the ASCP time is expected to rise over 40-50 min, bilateral cerebral perfusion is the technique that is best documented to be safe.

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 μg/l. D-dimers values were above 400 μg/l in 50 patients (82%) and below 400 μg/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.

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.

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.

Myocardial protection during aortic surgery: comparison between Bretschneider-HTK and cold blood cardioplegia.

The ideal cardioplegic strategy in thoracic aorta operations requiring long cardiopulmonary bypass and cross-clamp time has not been established. Suboptimal myocardial protection may lead to myocardial damage and possible post-operative complications. We evaluate post-operative cardiac Troponin I (cTnI) release, low cardiac output syndrome (LCOS) and mortality, using a cold crystalloid single-dose intracellular or cold blood multidose cardioplegia in 112 elective or emergent thoracic aorta operation patients. Fifty-four patients (HTK group) received Custodiol® cardioplegic solution and 58 received cold blood cardioplegia (CB group). Cross-clamp time, cardiopulmonary bypass (CPB) time and cTnI peak release were similar in both groups. No differences were found for atrial and ventricular arrhythmias, inotropic support, LCOS and in-hospital mortality. Two-way ANOVA analysis revealed an interactive effect on cTnI peak (p=0.012) of cardioplegic solution type across the cross-clamp time quintile. In the fifth quintile, cross-clamp time patient (>160 min) cTnI peak value was higher in CB patients (p=0.044). HTK and CB cardioplegic solutions assure similar myocardial protection in patients undergoing thoracic aorta operations. In long cross-clamp times, the lower post-operative cTnI release detected using HTK may be indicative of a better myocardial protection in these extreme conditions.

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.

Incremental Value of Anemia in Cardiac Surgical Risk Prediction With the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II Model

BACKGROUND Anemia is a risk factor for adverse events after cardiac operations. We evaluated the incremental value of preoperative anemia over the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II to predict hospital death after cardiac operations. METHODS Data for 4,594 consecutive adults (1,548 women [33.7%]), aged 67 ± 11 years, who underwent cardiac operations from January 2011 to July 2013 were extracted from the Regional Cardiac Surgery Registry of Puglia. The last preoperative hemoglobin value was used, according to World Health Organization criteria, to classify anemia as mild (hemoglobin 11.0 to 12.9 g/dL in men and 11.0 to 11.9 g/dL in women) in 1,021 patients (22.2%) and as moderate to severe (hemoglobin <11.0 g/dL) in 593 patients (12.9%). The EuroSCORE II was used to evaluate predicted hospital death after operations. Logistic regression analysis for in-hospital death was performed including EuroSCORE II risk factors and anemia, with model discrimination quantified by C statistic and risk classification by the use of net reclassification improvement (NRI). RESULTS Overall expected and observed mortality rates were 4.4% and 5.9%. Anemia was significantly associated with a mortality rate of 3.4% in patients without anemia, 7.7% in mild anemia, and 15.7% in moderate to severe anemia (p < 0.001) and also at multivariate analysis correcting for EuroSCORE II (p < 0.001). When anemia was analyzed with EuroSCORE II, the model improved in discrimination (C statistic = 0.852 vs 0.860; p = 0.007) and reclassification (category free-NRI, 0.592; p < 0.001), preserving the calibration with good concordance between predicted probabilities and outcome. CONCLUSIONS Preoperative anemia has strong association with operative death in cardiac surgical patients. Anemia provides significant incremental value over the EuroSCORE II and should be considered for assessment of cardiac surgical risk.

Pump blood processing, salvage and re-transfusion improves hemoglobin levels after coronary artery bypass grafting, but affects coagulative and fibrinolytic systems

Cell saving systems are commonly used during cardiac operations to improve hemoglobin levels and to reduce blood product requirements. We analyzed the effects of residual pump blood salvage through a cell saver on coagulation and fibrinolysis activation and on postoperative hemoglobin levels. Thirty-four elective coronary artery bypass graft (CABG) patients were randomized. In 17 patients, residual cardiopulmonary bypass (CPB) circuit blood was transfused after the cell saving procedure (cell salvage group). In the other 17 patients, residual CPB circuit blood was discarded (control group). Activation of the coagulative, fibrinolytic and inflammatory systems was evaluated pre-operatively (Pre), 2 hours after the termination of CPB (T0) and 24 hours postoperatively (T1), measuring prothrombin fragment 1.2 (PF 1.2), plasmin-anti-plasmin (PAP), plasminogen activator inhibitor-1 (PAI-1) and interleukin-6 (IL-6). The cell salvage group of patients had a significant improvement in hemoglobin levels after processed blood infusion (2.7 ± 1.7 g/dL vs 1.2 ± 1.1 g/dL; p=0.003). PF1.2 levels were significantly higher after infusion (T0: 1175 ± 770 pmol/L vs 730 ± 237 pmol/L; p=0.037; T1: 331 ± 235 pmol/L vs 174 ± 134 pmol/L; p=0.026). Also, PAP levels were higher in the cell salvage group, although not significantly (T0: 253 ± 251 ng/mL vs 168 ± 96 ng/mL; p: NS; T1: 95 ± 60 ng/mL vs 53 ± 32 ng/mL; p: NS). No differences were found for PAI-1, IL-6, heparin levels or for red blood cell (RBC) transfusions. The cell salvage group of patients had increased chest tube drainage (749 ± 320 vs 592 ± 264; p: NS) and fresh frozen plasma transfusion rate (5 (29%) pts vs 0 pts; p<0.04). Pump blood salvage with a cell saving system improved postoperative hemoglobin levels, but induced a strong thrombin generation, fibrinolysis activation and lower fibrinolysis inhibition. These conditions could generate a consumption coagulopathy.

Formation of anti-platelet factor 4/heparin antibodies after cardiac surgery: Influence of perioperative platelet activation, the inflammatory response, and histocompatibility leukocyte antigen status

BACKGROUND Anticoagulation therapy with heparin induces antibodies that recognize multimolecular complexes of platelet factor 4 bound to heparin (anti-platelet factor 4/heparin antibodies). Considering that cardiac surgery induces an intense platelet activation and proinflammatory response, we examined the relationship between formation of anti-platelet factor 4/heparin antibodies and plasma levels of platelet factor 4 and interleukin 6. We also examined the relationship between anti-platelet factor 4/heparin seroconversion and the histocompatibility leukocyte antigen system. METHODS In 71 patients undergoing cardiac surgery, anti-platelet factor 4/heparin antibody levels were evaluated by means of enzyme-linked immunosorbent assay preoperatively and 14 days postoperatively. Platelet serotonin release assays were performed to assess the platelet-activating potential of the antibodies. Plasma levels of platelet factor 4 and interleukin 6 were assayed at prespecified time points. Histocompatibility leukocyte antigen status was assessed preoperatively in all patients and was compared with that of 6156 healthy subjects. RESULTS Thirty-seven (52%) patients had anti-platelet factor 4/heparin antibodies with an OD value of 0.45 or greater in 1 or more of the assays. Applying strict seroconversion criteria (>2-fold increase in Optical Density), only 16 (22.5%) patients had evidence of anti-platelet factor 4/heparin antibody seroconversion after the operation. Neither the presence of anti-platelet factor 4/heparin antibodies nor seroconversion influenced postoperative outcomes. The CW4 allele was significantly more frequent among seroconverted patients (46.9% vs 19.1%, P = .002). Platelet factor 4 levels did not influence seroconversion. Patients with anti-platelet factor 4/heparin levels of 0.45 OD units or greater 14 days after the operation had significantly higher interleukin 6 levels measured 1 hour after protamine administration. DISCUSSION Patients with a greater amount of perioperative inflammation could be more likely to have anti-platelet factor 4/heparin antibodies 1 to 2 weeks later. We provide additional evidence that the histocompatibility leukocyte antigen CW4 confers genetic susceptibility in an acquired inflammatory disorder that includes the anti-platelet factor 4/heparin immune response.

Coagulation-Fibrinolysis Changes During Off-Pump Bypass: Effect of Two Heparin Doses

BACKGROUND To date, no study has tested the effect of different heparin dosages on the hemostatic changes during off-pump coronary artery bypass graft (OPCABG) surgery, and a wide variety of empirical anticoagulation protocols are being applied. We tested the effect of two different heparin dosages on the activation of the hemostatic system in patients undergoing OPCABG procedures. METHODS Forty-two patients eligible for OPCABG procedures were assigned in a randomized fashion to low-dose heparin (150 IU/kg) or high-dose heparin (300 IU/kg). Prothrombin fragment 1+2, plasmin/alpha(2)-plasmin inhibitor complex, D-dimer, soluble tissue factor, tissue factor pathway inhibitor, total thrombin activatable fibrinolysis inhibitor (TAFI), and activated TAFIa were assayed by specific enzyme-linked immunosorbent assays at six different timepoints, before, during, and after surgery. Platelet function was evaluated by means of an in vitro bleeding time test, platelet function analyzer-100. RESULTS The OPCABG surgery was accompanied by significant changes of all plasma biomarkers, indicative of systemic activation of coagulation and fibrinolysis. A significant increase in circulating TAFIa was detected perioperatively and postoperatively, and multiple regression analysis indicated that prothrombin F1+2 but not plasmin/alpha(2)-antiplasmin complex was independently associated with TAFIa level. Platelet function analyzer-100 values did not change significantly after OPCABG. All hemostatic changes were similar in the two heparin groups, even perioperatively, when the difference in anticoagulation was maximal. CONCLUSIONS Both early and late hemostatic changes, including TAFI activation, are similarly affected in the low-dose and high-dose heparin groups, suggesting that the increase in heparin dosage is not accompanied by a better control of clotting activation during OPCABG surgery.