Anna Cazzaniga

Predictors for heparin resistance in patients undergoing coronary artery bypass grafting

Heparin resistance (HR) is a common event in cardiac operations. At present, no clear recognition of the risk factors for HR has been reached. The aim of this study was to determine a predictive model for HR, based on the preoperative patient’s profile. Two hundred consecutive patients scheduled for elective coronary artery bypass operations were enrolled in a prospective trial. Demographics, type of preoperative anticoagulation therapy and preoperative coagulation profile were collected and statistically analysed with respect to the evidence of a HR. Heparin resistance was defined as at least one activated clotting time < 400 s after heparinization and/or the need for purified antithrombin III (AT-III) administration. With a multivariate analysis we could identify five predictors for HR: AT-III ≤ 60%; preoperative subcutaneous heparin therapy; intravenous heparin therapy; platelet count ≥ 300 000 cells/mm3; age ≥ 65 years. We conclude that HR is a predictable event. In the presence of all the risk factors, the likelihood of HR is 99%; in the absence of all of them, it is 10%. Predicting HR allows us to apply many possible therapeutic strategies.

Diabetes and complications after cardiac surgery: comparison with a non-diabetic population

Abstract Diabetes is a well-recognized independent risk factor for mortality due to coronary artery disease. When diabetic patients need cardiac surgery, either coronary-aortic by-pass (CABP) or valve operations (VO), the presence of diabetes represents an additional risk factor for these major surgical procedures. Because of controversial data on mortality rates and post-operative complications in diabetic patients, probably due to not exactly comparable groups of patients, this retrospective study aimed to compare two homogeneous populations, which were different only for the presence or absence of diabetes. We studied 700 patients undergoing cardiac surgery: 350 with and 350 without diabetes, mean age 62 ± 9 years (67% males); 441 underwent CABP and 259 VO. Apart from the diabetes, the two groups were strictly matched for age, body mass index, concomitant pathologies and smoking habits, except for previous neurological injuries (more frequent in diabetic patients), and for a slightly lower ejection fraction in the diabetic group. Intra- and post-operative complications or events were evaluated carefully: death, number staying in post-operative intensive care unit (ICU), renal, hepatic and respiratory complications, necessity for reoperation and hemotransfusions. Anesthesia and surgical procedures (including extra-coproreal circulation techniques) remained substantially unchanged over the period of recruitment of patients (1996–1998) and applied equally to both groups of patients. All diabetic patients were treated with insulin by using standard procedures in order to optimize metabolic control. Diabetic patients in our study, did not show higher rates of mortality in comparison with non-diabetic patients, but had more total neurological complications, more renal complications, a higher re-opening rate, more prolonged ICU stay, and they needed more blood transfusions. Diabetes remains an independent risk factor for these events even in a multivariate logistic regression model analysis. In the subgroup of diabetic patients who underwent CABP a higher rate of renal dysfunction, re-opening, need for hemotransfusions and prolonged ICU stay were confirmed. In the subgroup of diabetic patients undergoing VO we found a higher rate of renal dysfunction, reopening, prolonged ICU stay and major lung complications. In conclusion, diabetes does not seem to increase the mortality rates of cardiac surgery, but diabetic patients undergoing CABP have, on the basis of the relative risk evaluation, a 5-fold risk for renal complications, a 3.5-fold risk for neurological dysfunction, a double risk of being hemotransfused, reoperated or being kept 3 or more days in the ICU in comparison with non-diabetic patients. Moreover, diabetic patients undergoing VO have a 5-fold risk of being affected by major lung complications.

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.

Obesity and coronary artery surgery

OBJECTIVE To assess whether obesity is a risk factor for morbidity and mortality in patients undergoing elective coronary artery revascularization. DESIGN Prospective, clinical study. SETTING University hospital. PARTICIPANTS Three hundred forty-five consecutive patients who underwent elective coronary revascularization with cardiopulmonary bypass and without associated procedures. INTERVENTIONS Patients were assigned to the obese group if their body mass index was greater than 30 for men and 28.6 for women, according to the World Health Organization indications. MEASUREMENTS AND MAIN RESULTS Preoperative and intraoperative variables were collected and checked for homogeneity of the groups. Postoperative outcome was assessed on the basis of intubation time, intensive care unit (ICU) and postoperative hospital stay, mortality rate, and incidence of transfusions, reoperations, low-output syndrome, minor and major neurologic dysfunction, minor and major lung dysfunctions, renal dysfunction, and superficial and deep infections. The effect of obesity on postoperative outcome was tested with a multivariate logistic regression analysis. Obese and control patients had the same intubation time and ICU and postoperative hospital stay. Mortality and all major complications occurred with the same incidence in the two groups. Obese patients had a significantly (p < 0.05) greater rate of superficial infections and more (24.1% v 7.4%; p < 0.001) minor lung complications. Conversely, they had a significantly lower transfusion rate (27.5% v42.7%; p < 0.01). CONCLUSION Obese patients had only minor complications after coronary artery surgery. The large body surface area because of obesity protects them against the hemodilution-related transfusion risk.

Ontogenesis of α- and β-receptors located on cerebral microvessels

Abstract Adrenergic receptors in rat brain microvessels were studied during ontogenesis. Microvessels were prepared by albumin floatation and glass bead filtration techniques from cortices of 10-, 20- and 90-day-old rats. The lower level of α1- α2- and β-receptor sites observed in early life may correlate with the lower capacity of cerebral vascular regulatory mechanism in this period.

l-Arginine therapy in Raynaud's phenomenon?

SummarySincel-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects ofl-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynauds phenomenon. After therapy, patients withu Raynauds phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.

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.

Validation of renal-risk models for the prediction of non-renal replacement therapy cardiac surgery-associated acute kidney injury

BACKGROUND Cardiac surgery-associated acute kidney injury (AKI) is a serious complication of cardiac surgery, even when renal replacement therapy (RRT) is not required. The existing risk models for cardiac surgery associated AKI are designed to predict AKI requiring RRT (RRT-AKI). The aim of this study is to validate three risk models for the prediction of RRT-dependent and non-RRT AKI after cardiac surgery. METHODS Retrospective analysis on 7675 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for stage 1 and 2. RRT AKI and non-RRT AKI were defined according to the need for RRT. Three risk models were validated separately for RRT and non-RRT AKI: the Cleveland Risk Score, the Bedside Risk Score, and the Simplified Renal Index Scoring Scheme. Discrimination power was assessed with Receiver Operating Characteristics analysis and c-statistics. RESULTS There were 502 (6.5%) non-RRT AKI events, 128 (1.7%) RRT-AKI events, and 7045 (91.8%) no-events. The three models performed well for predicting RRT-AKI (c-statistics 0.75-0.79) and poorly for predicting non-RRT AKI (c-statistics 0.54-0.59). The models had an excellent calibration for RRT-AKI but not for non-RRT AKI. Preoperative serum creatinine and estimated glomerular filtration rate were associated with RRT AKI but not with non-RRT AKI. Mortality was 12.2% in non-RRT AKI and 46.9% in RRT-AKI, significantly (P = 0.001) higher than in patients without AKI (1.3%). CONCLUSIONS The existing risk models are inadequate for predicting non-RRT AKI following cardiac surgery, both in terms of discrimination and calibration.