Increased preoperative thrombin generation and low protein S level associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting.

In a previous study, preoperative levels of activated protein C (APC) were associated with unfavorable postoperative hemodynamics after coronary artery bypass grafting (CABG). Protein C is activated by thrombin. Protein S, the cofactor of activated protein C, has activated protein C-independent anticoagulant activity and cytoprotective effects. Therefore, the objective of this study was to test whether preoperative, baseline levels of either thrombin or protein S were associated with hemodynamic performance or markers of myocardial damage after CABG. One hundred patients undergoing elective on-pump CABG were prospectively studied. Prothrombin fragment F1+2 (a marker of thrombin generation) and free protein S were measured preoperatively and cardiac index, systemic vascular resistance index (SVRI), and pulmonary vascular resistance index (PVRI) were measured serially thereafter at fixed time points. Cardiac biomarkers CK-MBm and TnT were measured postoperatively. There was an inverse correlation between preoperative F1+2 and free protein S levels (r= -0.30, p=0.003). High preoperative F1+2 and low preoperative protein S levels were associated with a less favorable hemodynamic profile postoperatively. Patients with F1+2 in the highest decile (≥0.85 nmol/l) and patients with preoperative protein S in the lowest decile (≤63%) had lower CI values, and higher pulmonary and systemic vascular resistance index values postoperatively than comparison patients. Preoperative F1+2 or protein S did not correlate with postoperative cardiac biomarker levels. Baseline activation of coagulation and the balance between pro-coagulant and anti-coagulant factors preoperatively might have implications for postoperative hemodynamic recovery after CABG.

Comparison of the effect of 6% hydroxyethyl starch and gelatine on cardiac and stroke volume index: a randomized, controlled trial after cardiac surgery.

BACKGROUND AND AIMS: The objective of this study was to find out the effect of various doses of hydroxyethyl starch (HES), gelatine or Ringer's acetate on cardiac and stroke volume index after cardiac surgery. MATERIAL AND METHODS: Three consecutive boluses (each 7 mL·kg(-1)) of either 6% HES 130/0.4, 4% gelatine, or Ringer's acetate solutions were administered to 45 patients postoperatively. The rate of infusions was adjusted according to haemodynamic measurements. Thereafter, infusion of the study solution (7 mL·kg(-1)) was continued for the following 12 hours. The total dose of study solution was 28 mL·kg(-1). RESULTS AND CONCLUSION: Mean (SD) cardiac and stroke volume indices were greater in the HES group [2.8 L·min(-1)·m(-2) (0.7), 34.1 (6.7) ml·m( -2)] than in the gelatine group [2.2 L·min(-1)·m( -2) (0.6), 25.8 (7.2) ml·m(-2)] after completion of 7 mL·kg(-1) of study solution. At this stage, the effect of gelatine did not differ from Ringer's acetate. After completion of 14 mL·kg(-1) and 21 mL·kg(-1) of colloids, similar cardiac and stroke volume indices were observed and the haemodynamic response was better in both colloid groups than in the Ringer's acetate group. No differences between groups were detected on the first postoperative morning. In the early postoperative phase after cardiac surgery, the effect of a single dose of HES solution on the haemodynamics was superior to the effect of gelatine or Ringer's acetate. However, after repeated administration of the study solutions, the haemodynamics in the two colloid groups appeared to be similar, but superior to the Ringer's acetate group.

Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function.

BACKGROUND: Levosimendan is a compound with vasodilatory and inotropic properties. Experimental data suggest effective reversal of stunning and cardioprotective properties. METHODS: This prospective, randomized, placebo-controlled, double-blind study included 60 patients with 3-vessel coronary disease and left ventricular ejection fraction (LVEF) of less than 0.50. Levosimendan administration (12 microg/kg bolus, followed by an infusion of 0.2 microg/kg/min) was started immediately after induction anesthesia. Predefined strict hemodynamic criteria were used to assess the success of weaning. If weaning was not successful, CPB was reinstituted and an epinephrine infusion was started. If the second weaning attempt failed, intraaortic balloon pumping (IABP) was instituted. RESULTS: The groups had comparable demographics. The mean (standard deviation) preoperative LVEF was 0.36 (0.8) in both groups. The baseline cardiac index was 1.8 (0.3) L/min/m(2) in the levosimendan group and 1.9 (0.4) L/min/m(2) in the placebo group. The mean duration of CPB to primary weaning attempt was 104 (25) minutes in the levosimendan and 109 (22) minutes in the placebo group. Primary weaning was successful in 22 patients (73%) in the levosimendan group and in 10 (33%) in the placebo group (p = 0.002). The odds ratio for failure in primary weaning was 0.182 (95% confidence interval, 0.060 to 0.552). Four patients in the placebo group failed the second weaning and underwent IABP compared with none in the levosimendan group (p = 0.112). CONCLUSIONS: Levosimendan significantly enhanced primary weaning from CPB compared with placebo in patients undergoing 3-vessel on-pump coronary artery bypass grafting. The need for additional inotropic or mechanical therapy was decreased.

Outcome of aortic valve replacement with bioprostheses in the elderly.

BACKGROUND AND AIM OF THE STUDY: Today, the elderly population continues to increase worldwide, and rates of aortic stenosis (AS) climb with age. Since aortic valve replacement (AVR) is the current treatment for elderly patients with symptomatic AS, the number of patients undergoing AVR is expected to grow. METHODS: Among patients operated on at Helsinki University Hospital between 1992 and 1997, a cohort (n = 145) was followed after AVR with a bioprosthesis. The patients were allocated to three groups, based on their age at the time of surgery: > or = 80 years (n = 30), < 80 to > or = 70 years (n = 94), and < or = 70 years (n = 21). All data relating to preoperative risk factors were collected. A control examination, which included echocardiography, was performed at least five years after surgery, and the follow up was continued until July 2006. The number of deaths and causes of death, as well as valve-related complications, were noted. RESULTS: The 30-day mortality rates were 3.3% in the oldest (> or = 80-year) group, 6.4% in the middle (< 80 to > or = 70-year) group, and zero in the youngest (< or = 70-year) group. The mean age at death was 88 and 81 years in the oldest and middle groups, respectively. In the oldest and youngest groups, there were no reoperations, but five valve-related reoperations were performed during follow up in the middle group. At the control visit, the left ventricular ejection fraction was > 60% in all groups. In the oldest and middle groups the aortic valve gradient was lower than the preoperative level, while the left ventricular diameters and wall dimensions were smaller (p < 0.05). Valve calcification was observed in one patient in the youngest group. CONCLUSION: Elderly patients who had undergone AVR with a bioprosthesis had a good outcome after more than 10 years of follow up, with an improved cardiac function being preserved for at least seven years after surgery. Despite a severely impaired preoperative aortic valve function, octogenarians especially had a good life expectancy, possibly due to their low comorbidity rates. Hence, AVR with a bioprosthesis proved to be an excellent treatment in this patient group.

Rapidly degradable hydroxyethyl starch solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: There is continuing concern about the effect of hydroxyethyl starch (HES) solutions on blood coagulation. Rapidly degradable HES solutions with more favorable effects on clot strength have therefore been developed. Because the risk of bleeding is increased after cardiopulmonary bypass, we examined whether these types of HES solutions could be administered after cardiac surgery without an alteration of coagulation. METHODS: Two new rapidly degradable HES solutions were compared with human albumin in 45 patients scheduled for elective primary cardiac surgery. After admission to the cardiac surgical intensive care unit, the patients were allocated in random order to receive either 15 mL/kg of HES solution with low molecular weight and low molar substitution (either 6% HES200/0.5 or 6% HES130/0.4) or 4% human albumin solution as a short-time (70-240 min) infusion. RESULTS: Clot formation time was prolonged and maximum clot firmness was decreased in thromboelastometry tracings after infusion of both HES solutions. This impairment in thromboelastometry tracings partly recovered (using InTEM and ExTEM coagulation activators) at 2 h after the completion of the study infusion. Platelet contribution to maximum clot firmness remained unaffected in all of the study groups. HES did not induce fibrinolysis. No changes in thromboelastometry tracings were observed after human albumin infusion. Chest tube drainage was comparable in the study groups. CONCLUSIONS: We conclude that a short-time infusion of rapidly degradable HES solutions after cardiac surgery produces impairment in fibrin formation and clot strength in thromboelastometry tracings. In this clinical setting, human albumin does not impair hemostasis.

Tranexamic acid does not correct the haemostatic impairment caused by hydroxyethyl starch (200 kDa/0.5) after cardiac surgery.

We investigated the effect of intravenous tranexamic acid on hydroxyethyl starch (HES)-induced clot strength impairment after cardiac surgery. Patients were randomized to receive either 1 g tranexamic acid or the same volume of 0.9% saline after administration of 15 ml/kg of 6% HES (molecular weight, 200 kDa; degree of substitution, 0.5) in the immediate postoperative period. Modified thromboelastometry (ROTEM) using different activators [intrinsic ROTEM (InTEM), extrinsic ROTEM (ExTEM), fibrinogen ROTEM (FibTEM)] was carried out to evaluate clot formation and lysis. The clot formation time was prolonged, and the maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF / (100-MCF), dynes/cm(2)] decreased (all activators of ROTEM) after completion of HES (P < 0.001, two-factor analysis of variance). These abnormalities in blood coagulation persisted despite tranexamic acid. Maximal lysis (FibTEM), indicative of fibrinolytic activity, was increased after HES but no effect of tranexamic acid was observed. The cumulative chest tube drainage until the first postoperative morning was not different between the groups (1008 +/- 251 and 1081 +/- 654 ml, P = 0.698, respectively). We conclude that after cardiopulmonary bypass, HES-induced impairment in clot formation and strength, or increased fibrinolytic capacity, is not reversed by the administration of tranexamic acid.

Levosimendan reversing low output syndrome after heart transplantation.

After heart transplantation primary graft failure is a major cause of early mortality. Treatment options include inotropes and mechanical assist devices. Developing better methods would impact on patients' short- and long-term survival. We present a case of primary graft failure manifested as cardiogenic shock unresponsive to catecholamines and a phosphodiesterase inhibitor. Reversal of low output syndrome was achieved with a new type of inotropic agent, levosimendan, leading to the later complete recovery.

Predictive factors of hemodynamic collapse after coronary artery bypass grafting: a case-control study.

OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG) surgery is a complication with high morbidity and mortality. The aim of this study was to explore factors possibly predictive of this major complication. DESIGN: Retrospective case-control study. SETTING: University hospital, department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of 8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively matched patients (by age, sex, New York Heart Association classification, number of diseased vessels, left ventricular ejection fraction, and diabetes) served as a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular collapse underwent emergency reopening of the sternotomy and open cardiac massage (OCM group). Several pre-, intra-, and postoperative variables were compared, and significant parameters in match-pair analysis were further tested with regression techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76) versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group, cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH, p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients more frequently required postoperative inotropic (epinephrine, p = 0.0002) and mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis revealed a correlation between cardiopulmonary resuscitation risk and low cardiac index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue perfusion, postoperative myocardial ischemia, and increased need for inotropic and mechanical support preceded hemodynamic collapse. Interventions to improve tissue perfusion and to prevent and treat myocardial ischemia may result in a more favorable outcome.

Gelatin and hydroxyethyl starch, but not albumin, impair hemostasis after cardiac surgery.

We investigated the effect of postoperative administration of colloids on hemostasis in 45 patients after cardiac surgery. Patients were randomized to receive 15 mL kg(-1) of either 4% albumin, 4% succinylated gelatin, or 6% hydroxyethyl starch (molecular weight of 200 kDa/degree of substitution 0.5) as a short-term infusion. There was a comparable decrease in maximum clot firmness of thromboelastometry tracings in gelatin and hydroxyethyl starch groups immediately after completion of the infusion, whereas these values remained unchanged in the albumin group. The impairment in clot strength persisted up to 2 h, although the values partly recovered. Postoperative bleeding correlated inversely with the clot strength in pooled data of the artificial colloids. Fibrin formation (clot formation time, alpha-angle) and fibrinogen-dependent clot strength (maximum clot firmness and shear elastic modulus) were more disturbed in the hydroxyethyl starch group than in the gelatin group. We conclude that after cardiopulmonary bypass surgery, both gelatin and hydroxyethyl starch impair clot strength and fibrin buildup, which may predispose patients to increased blood loss. The greatest impairment in hemostasis was seen after hydroxyethyl starch administration, whereas albumin appeared to have the least effect on hemostatic variables.