Simonetta Brozzi

Postoperative antithrombin levels and outcome in cardiac operations

Objective:During cardiac operations with cardiopulmonary bypass surgery, antithrombin is consumed and low levels of antithrombin activity are commonly observed at admission to the intensive care unit (ICU). This study investigates the association between antithrombin activity at admission to the ICU (ICU-antithrombin activity) and various outcome variables. Design:The authors conducted a prospective, observational cohort study. Setting:The study was conducted at a university hospital. Patients:The study consisted of 647 consecutive patients who had undergone cardiac surgery with cardiopulmonary bypass. Measurements and Main Results:ICU-antithrombin activity significantly (p < .001) decreased with respect to preoperative values. As seen with univariate analysis, low levels of ICU-antithrombin activity were significantly associated with higher blood loss, prolonged mechanical ventilation time and ICU stay, a higher incidence of allogeneic blood products use, surgical reexploration, low cardiac output syndrome, adverse neurologic events, thromboembolic events, renal dysfunction, and hospital mortality. When corrected for the other explanatory variables, low levels of ICU-antithrombin activity remained independently associated with a prolonged ICU stay (p = .003) and with a higher incidence of surgical reexploration (p = .023), adverse neurologic events (p = .001), and thromboembolic events (p = .036). An ICU-antithrombin activity value of <58% was found to be predictive of prolonged ICU stay, with a sensitivity of 67% and a specificity of 83%. Conclusions:Low levels of ICU-antithrombin activity are associated with a poor outcome in cardiac surgery; ICU-antithrombin activity is predictive of prolonged ICU stay.

Different patterns of heparin resistance: therapeutic implications.

Heparin resistance (HR) during cardiac operations is a common feature. Its aetiology often recognizes a decrease in circulating antithrombin III (AT III) due to a preoperative heparin treatment. Nevertheless, some papers highlighted the existence of HR in patients with normal values of AT III. This paper was designed in order to identify this subgroup of AT III-independent heparin-resistant patients. Five hundred consecutive patients scheduled for coronary revascularization with cardiopulmonary bypass were enrolled in this prospective trial. HR was identified in 104 (20.8%) patients. Thirty-six of them (7.2% of the total population) had a preoperative AT III activity ≥100%, and were defined as AT III-independent heparin-resistant patients. This subgroup significantly differs from the AT III-dependent heparin-resistant group being affected by a less severe degree of HR and including less patients pretreated with heparin. Unlike the other heparin-resistant patients, these subjects do not respond to AT III supplementation aimed at reaching supranormal AT III activity values.

A Systematic Review of Biocompatible Cardiopulmonary Bypass Circuits and Clinical Outcome

This systematic review and meta-analysis explores the clinical efficacy of biocompatible surfaces for cardiopulmonary bypass in adults. Thirty-six randomized controlled trials were retrieved for a total of 4360 patients. Patients treated with biocompatible circuits had a lower rate of packed red cells transfusions and atrial fibrillation, and shorter durations of stay in the intensive care unit. When the analysis was limited to high-quality studies, only a reduction in atrial fibrillation rate and a shorter stay in the intensive care unit remained significantly associated with the use of biocompatible surfaces. Using biocompatible surfaces without other measures to contain blood activation results in a limited clinical benefit.

Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood

IntroductionCardiac surgery using cardiopulmonary bypass in newborns, infants and small children often requires intraoperative red blood cell transfusions to prime the circuit and oxygenator and to replace blood lost during surgery. The purpose of this study was to investigate the influence of red blood cell storage time prior to transfusion on postoperative morbidity in pediatric cardiac operations.MethodsOne hundred ninety-two consecutive children aged five years or less who underwent cardiac operations using cardiopulmonary bypass and who received red blood cells for priming the cardiopulmonary bypass circuit comprised the blood-prime group. Forty-seven patients receiving red blood cell transfusions after cardiopulmonary bypass were separately analyzed. Patients in the blood-prime group were divided into two groups based on the duration of storage of the red blood cells they received. The newer blood group included patients who received only red blood cells stored for less than or equal to four days and the older blood group included patients who received red blood cells stored for more than four days.ResultsPatients in the newer blood group had a significantly lower rate of pulmonary complications (3.5% versus 14.4%; P = 0.011) as well as a lower rate of acute renal failure (0.8% versus 5.2%; P = 0.154) than patients in the older blood group. Major complications (calculated as a composite score based on pulmonary, neurological, and gastroenterological complications, sepsis and acute renal failure) were found in 6.9% of the patients receiving newer blood and 17.1% of the patients receiving older blood (P = 0.027). After adjusting for other possible confounding variables, red blood cell storage time remained an independent predictor of major morbidity. The same association was not found for patients receiving red blood cell transfusions after cardiopulmonary bypass.ConclusionsThe storage time of the red blood cells used for priming the cardiopulmonary bypass circuit in cardiac operations on newborns and young infants is an independent risk factor for major postoperative morbidity. Pulmonary complications, acute renal failure, and infections are the main complications associated with increased red blood cell storage time.

Determinants of antithrombin consumption in cardiac operations requiring cardiopulmonary bypass

Antithrombin (AT) is a natural anticoagulant that is consumed during cardiac operations with cardiopulmonary bypass (CPB). This study is an observational trial aimed at identifying the factors determining the magnitude of the AT consumption during cardiac operations. Two hundred and fifty consecutive adult patients undergoing cardiac operations with CPB were admitted to the study. Preoperative and intraoperative variables were tested with respect to their role in determining AT activity at the end of the operation. At a univariate analysis, eight predictors of AT activity at the end of the operation have been identified: preoperative AT activity; age; diabetes on medication; preoperative haematocrit value; preoperative dialysis; combined operation; CPB duration; lowest temperature on CPB. A multivariate predictive model was created, and five factors remained as independent predictors of AT activity at the end of the operation: preoperative AT activity (p = 0.001); age (p = 0.015); combined operation (p = 0.014); diabetes (p = 0.013) and CPB duration (p = 0.001). On this basis, predictive tables of AT consumption have been established for different combinations of risk factors.

Pre-operative homocysteine levels and morbidity and mortality following cardiac surgery

Aims Elevated homocysteinaemia is associated not only with an increased risk for cardiovascular disease but also for increased morbidity and mortality in patients with established coronary artery or cerebrovascular disease. Whether elevated homocysteine further increases the morbidity and mortality in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) (a prothrombotic state itself) remains less known. Methods and results Accordingly, we conducted a prospective observational study with pre-operative measurement of plasma homocysteine levels in 531 consecutive patients undergoing cardiac operations on CPB. The association of pre-operative plasma homocysteine levels with post-operative morbidity and hospital mortality was evaluated. Elevated homocysteine levels (>15 µmol/L) were observed in 209 patients (39.4%), and homocysteinaemia was associated with a higher mortality and perioperative morbidity (major morbidity, low cardiac output, acute renal failure, mesenteric infarction, and thrombo-embolic events). Even after accounting for the differences in baseline clinical features, EuroSCORE, and CPB time, pre-operative homocysteine levels remained independently associated with hospital mortality [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03–1.11], major morbidity (OR 1.04, 95% CI 1.01–1.07), low cardiac output (OR 1.04, 95% CI 1.02–1.08), mesenteric infarction (OR 1.06, 95% CI 1.01–1.11), and thrombo-embolic events (OR 1.09, 95% CI 1.04–1.13). This association of homocysteine with increased risk of morbidity and mortality was observed particularly in CABG patients. Conclusion Elevated pre-operative homocysteine level is independently associated with increased morbidity and mortality, particularly in patients undergoing CABG. Specific post-operative antithrombotic strategies may be advisable in hyperhomocysteinaemic patients.

Intensive Care Unit Admission Parameters Improve the Accuracy of Operative Mortality Predictive Models in Cardiac Surgery

Background Operative mortality risk in cardiac surgery is usually assessed using preoperative risk models. However, intraoperative factors may change the risk profile of the patients, and parameters at the admission in the intensive care unit may be relevant in determining the operative mortality. This study investigates the association between a number of parameters at the admission in the intensive care unit and the operative mortality, and verifies the hypothesis that including these parameters into the preoperative risk models may increase the accuracy of prediction of the operative mortality. Methodology 929 adult patients who underwent cardiac surgery were admitted to the study. The preoperative risk profile was assessed using the logistic EuroSCORE and the ACEF score. A number of parameters recorded at the admission in the intensive care unit were explored for univariate and multivariable association with the operative mortality. Principal Findings A heart rate higher than 120 beats per minute and a blood lactate value higher than 4 mmol/L at the admission in the intensive care unit were independent predictors of operative mortality, with odds ratio of 6.7 and 13.4 respectively. Including these parameters into the logistic EuroSCORE and the ACEF score increased their accuracy (area under the curve 0.85 to 0.88 for the logistic EuroSCORE and 0.81 to 0.86 for the ACEF score). Conclusions A double-stage assessment of operative mortality risk provides a higher accuracy of the prediction. Elevated blood lactates and tachycardia reflect a condition of inadequate cardiac output. Their inclusion in the assessment of the severity of the clinical conditions after cardiac surgery may offer a useful tool to introduce more sophisticated hemodynamic monitoring techniques. Comparison between the predicted operative mortality risk before and after the operation may offer an assessment of the operative performance.

Effects of priming volume reduction on allogeneic red blood cell transfusions and renal outcome after heart surgery

Introduction: Excessive hemodilution during cardiopulmonary bypass (CPB) is associated with an increased rate of red blood cell (RBC) transfusion and acute kidney injury (AKI). Minimization of the oxygenator priming volume is a measure to contain hemodilution. In this study, we evaluated the new oxygenator, Sorin Inspire 6™, with respect to its ability to limit hemodilution, RBC transfusion rate and postoperative AKI rate. Methods: A retrospective study on a consecutive series of 1,724 adult patients receiving heart surgery with CPB. Patients treated with the Inspire 6™ were assigned to the low priming volume oxygenator (LPVO) group (N=383) and patients treated with conventional oxygenators to the conventional group (N=1,341). Dynamic priming volume, time course of the hematocrit, RBC transfusions and AKI rate were compared between the groups. Results: Priming volume was significantly (p=0.001) lower in the LPVO group (624±113 mL) vs. the conventional group (775±150 mL), with higher values of hematocrit during and after CPB. After correction for other confounders, patients in the LPVO group had a significantly lower RBC transfusion rate (odds ratio 0.68, 95% confidence interval 0.52-0.90, p=0.006) and AKI rate (odds ratio 0.55, 95% confidence interval 0.32-0.93, p=0.032). Conclusion: The Inspire 6™ oxygenator allows a significant containment of hemodilution during CPB, reducing the risk of RBC transfusions and postoperative AKI.

Transfusions during cardiopulmonary bypass: better when triggered by venous oxygen saturation and oxygen extraction rate

During cardiopulmonary bypass (CPB), red blood cell transfusions may be required to correct dilutional anemia. The decision-making process for transfusions is usually based on the level of hemoglobin.This study investigates the hypothesis that oxygen-derived variables (mixed venous oxygen saturation, SvO2, and oxygen extraction rate, O2ER) may be more reliable predictors of the efficacy of the transfusion. Thirty-six patients for 41 transfusion episodes during CPB were retrospectively analyzed. For each patient, oxygen-derived variables, including SvO2 and O2ER, were measured before and after the transfusion. No changes in pump flow were allowed between the two measurements. The efficacy of transfusion was defined as an increase in SvO2 of at least 5%. We identified 11 transfusion episodes leading to an efficacious SvO 2 increase. Factors associated with the efficacy of the transfusion were a low SvO2 and a high O2ER. No association was found with hemoglobin values, unless for a trend for efficacy of transfusion in patients with very low (<6 g/dL) hemoglobin values. Cut-off values of 68% for SvO2 and 39% for O2ER were predictive for the efficacy of red blood cell transfusions, with a high accuracy (c-statistics 0.856 and 0.848, respectively) and negative and positive predictive values exceeding 82%. In conclusion, SvO2 and O2ER are better than the hemoglobin value for guiding the decision-making process of red blood cell transfusions to correct hemodilutional anemia during CPB.

Gabexate mesilate and antithrombin III for intraoperative anticoagulation in heparin pretreated patients

Thirty patients scheduled for elective myocardial revascularization and having undergone preoperative heparin treatment have been admitted to this prospective, randomized study. The aim of the study was to test two different strategies for preserving circulating antithrombin III (AT-III) during cardiopulmonary bypass. Patients in the control group (group C, n = 10) were treated with a standard heparinization (300 IU/kg). Patients in group A (n = 10) received the same management plus two doses of purified antithrombin III (1000 IU each). Patients in group GA received 200 IU/kg heparin and a continuous infusion of heparin (100 IU/kg/h) and gabexate mesilate (2 mg/kg/h) plus the same dose of antithrombin III as group A. Both group A and group GA demonstrated a preservation of circulating AT-III when compared to group C; this effect was more pronounced in group GA. The total heparin dosage was less in group GA than in groups A and C. Purified AT-III administration is recommended in heparin pretreated patients; the addition of gabexate mesilate to this protocol decreases the heparin requirement and increases the AT-III preservation.