Domenico Vitale

Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery

BACKGROUND The calcium sensitizer levosimendan has anti-ischaemic effects mediated via the opening of sarcolemmal and mitochondrial ATP-sensitive potassium channels. These properties suggest potential application in clinical situations where cardioprotection would be beneficial, such as cardiac surgery. We thus decided to investigate whether pharmacological pre-treatment with levosimendan reduces intensive care unit (ICU) length of stay in patients undergoing elective myocardial revascularization under cardiopulmonary bypass. METHODS One hundred and six patients undergoing elective coronary artery bypass grafting were randomly assigned in a double-blind manner to receive levosimendan or placebo. Levosimendan (24 microg kg(-1)) or placebo was administered as a slow i.v. bolus over a 10 min period before the initiation of bypass. RESULTS Tracheal intubation time and the length of ICU stay were significantly reduced in the levosimendan group (P<0.01). The number of patients needing inotropic support for >12 h was significantly higher in the control group (18.0% vs 3.8%; P=0.021). Compared with control patients, levosimendan-treated patients had lower postoperative troponin I concentrations (P<0.0001) and a higher cardiac power index (P<0.0001). CONCLUSIONS Pre-treatment with levosimendan in patients undergoing surgical myocardial revascularization resulted in less myocardial injury, a reduction in tracheal intubation time, less requirement for inotropic support, and a shorter length of ICU stay.

Epicardial adipose tissue and intracoronary adrenomedullin levels in coronary artery disease.

The aim of the study was to test 1) whether chronic and stable coronary artery disease (CAD) could downregulate epicardial fat adrenomedullin synthesis and secretion, and decrease intracoronary plasma adrenomedullin levels, and 2) whether intracoronary plasma adrenomedullin levels could be related to epicardial adipose tissue adrenomedullin gene and protein expression in subjects with CAD. We examined 12 patients with CAD who required coronary artery bypass graft (CABG) and 10 patients with non-CAD who underwent cardiac surgery for valve replacement. Plasma levels of adrenomedullin were measured in peripheral vein circulation, in left coronary artery (LCA) and coronary sinus (CS) during coronary angiography. Epicardial adipose tissue biopsy for Reverse Transcription and Real-Time PCR (RT-PCR) adrenomedullin mRNA analysis and Western Blotting (WB) protein expression was performed during cardiac surgery in all subjects. Peripheral, LCA, and CS plasma adrenomedullin levels were significantly lower in CAD patients than in those with non-CAD (3.0+/-0.9 vs. 4.4+/-0.9 pg/ml p<0.01; 2.9+/-1 vs. 4.05+/-0.8 pg/ml, p<0.01, 3.1+/-0.9 vs. 3.98+/-0.9 pg/ml p=0.04, respectively). However, CS adrenomedullin levels were not statistically different than those in LCA suggesting that adrenomedullin was not secreted from epicardial fat into the coronary artery lumen. Epicardial fat adrenomedullin mRNA levels and protein expression were lower in patients with CAD than in those with non-CAD (p<0.01 for both). We conclude that 1) epicardial fat adrenomedullin gene and protein expression can be downregulated in CAD subjects, and 2) intracoronary adrenomedullin levels are lower in CAD. No evidence that epicardial adipose tissue really contributes intracoronary adrenomedullin can be provided at this time.

Recombinant activated factor VII for refractory bleeding after acute aortic dissection surgery: a propensity score analysis.

Objective:The aim of this study was to assess safety and effectiveness of recombinant activated factor VII (rFVIIa) in patients with refractory bleeding undergoing acute aortic dissection surgery with deep hypothermic circulatory arrest. Design:Propensity score-matched analysis. Setting:University hospital. Patients:Twenty-three cardiac surgery patients receiving rFVIIa compared with 23 matched controls. Interventions:An intravenous bolus of rFVIIa (70 &mgr;g/kg) was administered at the end of a complete transfusion protocol. Five patients received rFVIIa in the operating room, and 18 patients received rFVIIa in the intensive care unit. Four of the intensive care unit patients required a second dose. Measurements and Main Results:Blood loss and transfusion requirements were significantly reduced in the period after rFVIIa administration. A highly significant reduction in hourly blood loss was found at −1 hr vs. 0 hrs and 0 hrs vs. 1 hr (−194 and −77.5 mL, respectively; both adjusted p < .001). In addition, significant improvements of international normalized ratio (p < .001), partial thromboplastin time (p < .001), platelet count (p < .001), fibrinogen (p < .001), and antithrombin (p < .001) were detected after rFVIIa administration. The two groups did not differ regarding adverse events. Conclusions:rFVIIa was successfully used as an additional therapy both during and after acute aortic dissection surgery with deep hypothermic circulatory arrest, when bleeding was refractory to conventional methods. Randomized studies are necessary to confirm the safety and efficacy of rFVIIa in this setting.

Use of ivabradine in catecholamine-induced tachycardia after high-risk cardiac surgery

Low cardiac output syndrome commonly occurs after cardiac surgery with cardiopulmonary bypass (CPB) and often requires inotropic support to achieve an adequate hemodynamic status. The use of b-receptor stimulating substances is often needed in cardiac surgical patients to treat myocardial pump failure and subsequently prevent low output syndrome [1]. However, increased b-adrenergic stimulation may be associated with increased heart rate, myocardial oxygen consumption and incidence of dysrhythmias, especially in ischemic tissues or during reperfusion [2]. Ivabradine is a new molecule that specifically inhibits the funny current channels (If) in the sinoatrial node and reduces heart rate, without affecting other aspects of cardiac function [3]. In patients with stable coronary artery disease and left-ventricular systolic dysfunction, ivabradine reduced the incidence of admission to hospital for fatal and non-fatal myocardial infarction and coronary revascularization in a subgroup of patients who have heart rates of 70 bpm or greater [4, 5]. To our knowledge, no studies exist testing ivabradine in catecholamine-induced tachycardia after cardiac surgery. We present a case series of 15 patients who developed low cardiac output syndrome after cardiopulmonary bypass. Patient characteristics are presented in Table 1. A standardized anesthesia protocol was used for all patients. Routine monitoring included standard 8-lead electrocardiogram, radial artery pressure, thermodilution pulmonary artery catheter, and transesophageal echocardiography evaluation. Brain natriuretic peptide (BNP) levels were measured at baseline (before ivabradine administration) and at 24 h. Weaning from the CPB, maintenance of acceptable blood pressure ([60 mmHg) and targeted cardiac index (CI C 2.0 l/min/m) were achieved following a strict protocol. If target CI was not obtained, pulmonary capillary wedge pressure (PCWP) was first optimized with fluid administration up to 12–18 mmHg, and then inotropic support was started. Dobutamine was used as first-line inotropic agent, starting with 2 lg/kg/min and increasing the dose if necessary up to 10 lg/kg/min. If dobutamine failed to achieve acceptable CI, adrenaline was started with 0.03 lg/kg/min and increasing the dose if necessary up to 0.1 lg/kg/min. if low output persisted, an intra-aortic balloon pump was inserted. Mean arterial pressure (MAP) was maintained at C60 mmHg, with noradrenaline if needed. All the patients were on inotropic support and developed sinus tachycardia (HR [ 90 bpm). After 6 h from ICU admission, ivabradine was given via a nasogastric tube (starting dose 10 mg followed by a maintenance dose of 5 mg/12 h). Haemodynamic data are showed in Fig. 1. D. Vitale V. De Santis (&) L. Tritapepe Department of Anesthesiology and Intensive Care, ‘‘Sapienza’’ University of Rome, Viale Del Policlinico 155, 00161 Rome, Italy e-mail: vincenzo.desantis@uniroma1.it

Treatment with β-Blockers and Incidence of Post-Traumatic Stress Disorder After Cardiac Surgery: A Prospective Observational Study

OBJECTIVE The aim was to investigate perioperative factors associated with the development of post-traumatic stress disorder (PTSD) in patients who underwent cardiac surgery. DESIGN Prospective observational study. SETTING Single academic center. PARTICIPANTS One hundred twenty-eight consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS Patients were interviewed within the surgical unit 1 to 3 days before cardiac surgery. MEASUREMENTS AND MAIN RESULTS Six months after surgery, participants were mailed the modified version of the Posttraumatic Stress Symptom Inventory 10. Of the 71 patients who completed the questionnaire and mailed it back at follow-up, 14 (19.7%) received a diagnosis of PTSD. Seven of 13 female patients who were not treated with β-blockers received a diagnosis of PTSD compared with 0 of 12 who were treated with β-blockers (p = 0.005, Fisher exact test). In a general linear model, including sex and β-blocker treatment as predictors, the Posttraumatic Stress Symptom Inventory 10 score was significantly predicted by β-blockade (F = 4.74, p = 0.033), with a significant interaction between sex and β-blockade (F = 9.72, p = 0.003). CONCLUSIONS These findings suggest that the use of β-blockers might be protective against the development of PTSD in women after cardiac surgery.

2273 – Attachment style and posttraumatic stress disorder after cardiac surgery

Introduction Cardiac surgery with cardiopulmonary bypass represents a severe source of stress and has been reported to be associated to the development of Posttraumatic Stress Disorder (PTSD). This disorder leads to a significant disability that might greatly decrease the benefits of surgery. Research rarely focused on the role of attachment styles in the development of PTSD, and no studies addressed this issue in patients undergoing cardiac surgery. Objectives To assess the influence of attachment styles on the development of PTSD. Aims The identification of specific personological traits predictive of the development of PTSD. Methods Participants were recruited among patients scheduled for elective cardiac surgery with cardiopulmonary bypass and evaluated through a) Experiences in Close Relationships (ECR) b) Post-traumatic 10 Stress Symptom Inventory - Modified (PTSS-10) c) Perceived Stress Scale (PSS). Six months after surgery, participants were mailed the PTSS-10 and the PSS. Multiple logistic regression analysis was performed with PTSD as dependent variable, and attachment-related avoidance and anxiety, sex, age and perceived stress as independent variables. Results One hundred twenty-one patients (94% of candidates for elective cardiac surgery who met study inclusion criteria) underwent surgery; 61(59%) were assessed after 6 months. Fourteen subjects (19.7%) scored ≥35 on the PTSS-10 at followup and were considered as having a probable diagnosis of PTSD. Attachment related avoidance at baseline predicted the development of PTSD at follow-up (p Conclusions Subjects endorsing the avoidant attachment style are more likely to develop PTSD after cardiac surgery.