Desmopressin after cardiac surgery in bleeding patients. A multicenter randomized trial.

BACKGROUND: Previous studies showed that desmopressin decreases post-operative blood loss in patients undergoing cardiac surgery. These studies were small and never studied the effect of desmopressin in patients with active bleeding. Objective of the study was to determine whether desmopressin reduces red blood cells transfusion requirements in patients with active bleeding after cardiac surgery who had been pre-treated with tranexamic acid. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study randomized elective patients with bleeding after cardiac surgery despite pre-treatment with tranexamic acid, to receive placebo (saline solution) or a single administration of desmopressin (0.3 µg/kg in saline solution). The primary endpoint was the number of patients requiring red blood cells transfusion after randomization and during hospital stay. Secondary end points were: blood loss from chest tubes during the first 24 h after study drug administration, hours of mechanical ventilation, intensive care unit stay, and in-hospital mortality. RESULTS: The study was interrupted after inclusion of 67% of the planned patients for futility. The number of patients requiring red blood cells transfusion after randomization was 37/68 (54%) in desmopressin group and 33/67 (49%) in placebo group (P = 0.34) with no difference in blood loss: 575 (interquartile 422-770) ml in desmopressin group and 590 (476-1013) ml in placebo group (P = 0.42), mechanical ventilation, intensive care unit stay or mortality. CONCLUSIONS: This multicenter randomized trial demonstrated that, in patients pre-treated with tranexamic acid, desmopressin should not be expected to improve treatment of patients who experience bleeding after cardiac surgery.

Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study.

BACKGROUND: The effect of anaesthesia on postoperative outcome is unclear. Cardioprotective properties of volatile anaesthetics have been demonstrated experimentally and in haemodynamically stable patients undergoing coronary artery bypass grafting. Their effects in patients undergoing high-risk cardiac surgery have not been reported. METHODS: We performed a multicentre, randomized, parallel group, controlled study among patients undergoing high-risk cardiac surgery (combined valvular and coronary surgery) in 2008-2011. One hundred subjects assigned to the treatment group received sevoflurane for anaesthesia maintenance, while 100 subjects assigned to the control group received propofol-based total i.v. anaesthesia. The primary outcome was a composite of death, prolonged intensive care unit (ICU) stay, or both. Thirty day and 1 yr follow-up, focused on mortality, was performed. RESULTS: All 200 subjects completed the follow-up and were included in efficacy analyses, conducted according to the intention-to-treat principle. Death, prolonged ICU stay, or both occurred in 36 out of 100 subjects (36%) in the propofol group and in 41 out of 100 subjects (41%) in the sevoflurane group; relative risk 1.14, 95% confidence interval 0.8-1.62; P=0.5. No difference was identified in postoperative cardiac troponin release [1.1 (0.7-2) compared with 1.2 (0.6-2.4) ng ml(-1), P=0.6], 1 yr all-cause mortality [11/100 (11%) compared with 11/100 (11%), P=0.9], re-hospitalizations [20/89 (22.5%) compared with 11/89 (12.4%), P=0.075], and adverse cardiac events [10/89 (11.2%) compared with 9/89 (10.1%), P=0.8]. CONCLUSIONS: There was no observed beneficial effect of sevoflurane on the composite endpoint of prolonged ICU stay, mortality, or both in patients undergoing high-risk cardiac surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: identifier NCT00821262. Eudra CT (2008-001752-43).

Protein C zymogen in adults with severe sepsis or septic shock

INTRODUCTION: Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen. Design, setting and participants: A prospective study on 23 adult patients with severe sepsisor septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50 IU/kg bolus followed by continuous infusion of 3 IU/kg/h for 72 h).RESULTS: The Z-test evidenced a significant reduction between the expected mortality (53%)and the observed mortality 30% (Z value = 1.99, p = 0.046) in our sample population. Protein Clevels increased from 34 ± 18% to 66 ± 22% at 6 h after PC bolus (p < 0.001), and kept on increasing during 72 h of administration (p < 0.001 to baseline). Sequential Organ Failure Assessment(SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14 ± 2 to 7 ± 4 (p < 0.001). No adverse event drug related was noted. CONCLUSION: Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial

INTRODUCCIÓN: La proteína C activada se asocia a un elevado riesgo de hemorragia, y sus efectos sobre la supervivencia en los pacientes con choque séptico son cuestionables. El zimógeno de proteína C no presenta ningún riesgo de hemorragia, y mejora los resultados en los pacientes con choque séptico. Describimos la serie de casos más amplia publicada de pacientes adultos tratados con zimógeno de proteína C. Diseño, ámbito y participantes: Se ha llevado a cabo un estudio prospectivo en el que han articipado 23 adultos con sepsis grave o choque séptico, 2 o más fallos orgánicos, y un elevado riesgo de hemorragia, tratados con zimógeno de proteína C (dosis en bolo de 50 UI/kg seguida de una infusión continua de 3 UI/kg/h durante 72h). RESULTADOS: La prueba Z puso de manifiesto una disminución significativa entre la mortalidad prevista (53%), y la mortalidad observada 30% (valor Z = 1,99; p = 0,046) en nuestra serie. Las concentraciones de proteína C incrementaron de 34 ±18% a 66 ± 22% a las 6 h de la dosis en bolo (p < 0,001), y siguieron incrementando durante las 72 h siguientes a la administración (p < 0,001 respecto a la situación basal). La puntuación en la evaluación secuencial del fallo orgánico (SOFA) disminuyó entre la situación basal, y 7 días después de la administración de proteína C de 14 ± 2 a 7 ± 4 (p < 0,001). No se registraron reacciones farmacológicas adversas. CONCLUSIÓN: El zimógeno de proteína Z debería investigarse su utilización en los pacientes con sepsis mediante un estudio aleatorizado y controlado

Protein C zymogen in adults with severe sepsis or septic shock.

INTRODUCTION: Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen. DESIGN, SETTING AND PARTICIPANTS: A prospective study on 23 adult patients with severe sepsis or septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50IU/kg bolus followed by continuous infusion of 3IU/kg/h for 72h). RESULTS: The Z-test evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (Z value=1.99, p=0.046) in our sample population. Protein C levels increased from 34±18% to 66±22% at 6h after PC bolus (p<0.001), and kept on increasing during 72h of administration (p<0.001 to baseline). Sequential Organ Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14±2 to 7±4 (p<0.001). No adverse event drug related was noted. CONCLUSION: Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial.

Anesthetic management for percutaneous aortic valve implantation: an overview of worldwide experiences.

Transcatheter aortic valve implantation is an emergent technique for high risk patients with aortic stenosis. Transcatheter aortic valve implantation poses significant challenges about its management, due to the procedure itself (i.e. the passage of large stiff sheaths in diseased vessels, the valve dilatation and the prosthesis positioning during a partial cardiac standstill) and the population of elder and high-risk patients who undergo the implantation. Retrograde transfemoral approach is the most popular procedure and a great number of cases is reported. Nevertheless, there is not a consensus regarding the intraoperative anesthesiological strategies, which vary in the different Centers. Sedation plus local anesthesia or general anesthesia are both valid alternatives and can be applied according to patient's characteristics and procedural instances. Most groups started the implantation program with a general anesthesia; indeed, it offers many advantages, mainly regarding the possibility of an early diagnosis and treatment of potential complications, through the use of the transesophageal echocardiography. However, after the initial experiences, many groups began to employ routinely sedation plus local anesthesia for transcatheter aortic valve implantation and their procedural and periprocedural success demonstrates that it is feasible, with many possible advantages. Many aspects about perioperative anesthetic management for transcatheter aortic valve implantation are still to be defined. Aim of this work is to clarify the different management strategies through a review of the available literature published in pubmed till June 2011.

Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study.

BACKGROUND: Myocardial ischemic damage is reduced by volatile anaesthetics in patients undergoing low-risk coronary artery bypass graft surgery; few and discordant results exist in other settings. We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery. METHODS: Patients with coronary artery disease undergoing mitral surgery were randomly allocated to receive either sevoflurane (50 patients) or propofol (50 patients) as main hypnotic. The primary endpoint of the study was peak post-operative cardiac troponin release defined as the maximum value among the post-operative values measured at intensive care unit arrival, 4 h later, on the first and second post-operative day. RESULTS: There was no significant difference in post-operative peak troponin release, the median (25th-75th percentiles) values being 14.9 (10.1-22.1) ng/ml and 14.5 (8.8-17.6) ng/ml in the sevoflurane and propofol groups, respectively (P = 0.4). Fentanyl administration was different between the two groups: 1347 ± 447 µg in patients receiving sevoflurane and 1670 ± 469 µg in those receiving propofol, P = 0.002. The 1-year follow-up identified two patients who died in the propofol group (one myocardial infarction and one low cardiac output syndrome) and one in the sevoflurane group (myocardial infarction). CONCLUSION: In this study, patients with coronary artery disease undergoing mitral surgery did not benefit from the cardioprotective properties of halogenated anaesthetics. Sevoflurane anaesthesia was not associated to lower cardiac troponin release when compared with propofol anaesthesia.

Anesthesiological management and outcome of 100 ''beating heart'' coronary artery bypass grafting.

AIM: The aim of this paper is to describe the anesthesiological management and the outcome of beating heart revascularization. METHODS: A prospective study has been performed in a tertiary teaching hospital on 100 consecutive patients undergoing off-pump coronary artery revascularization. The main features of anesthetic technique are the maintenance hemodynamic stability and atrial kick. RESULTS: Mechanical stabilisers shunts have improved the management of these patients. In hospital mortality was 1%, acute myocardial infarction 3%, low output syndrome 2%, atrial fibrillation 16%. Only 2% of patients had acute renal failure, but no patient needed renal replacement treatment. No neurologic event was noted. Only 19% of patients received blood transfusion. Ninety-seven % of patients were extubated within 12 h. CONCLUSIONS: The application of this anesthetic strategy combined with surgical skillful and new devices makes off-pump surgery safe also in high risk patients.

Redo coronary artery bypass grafting on the beating heart and transfusion needs.

AIM: Reoperative coronary artery bypass grafting is associated with significant morbidity and a difficult perioperative management; in particular, important bleeding is observed. Off pump technique may give specific advantages in redo coronary operations since it is associated to decreased interactions of blood with foreign surfaces. We investigated our 5-year database to evaluate the role of off pump technique in reducing transfusion needs. METHODS: The present single centre case control study was carried out in a university tertiary care hospital on 132 consecutive patients undergoing reoperative coronary artery bypass grafting off pump (OP group, 41 patients) or with cardiopulmonary bypass (CPB group, 91 patients). Univariate and multivariate analysis were performed. RESULTS: There was no preoperative difference between the 2 groups; mean number of grafts per patient differed between groups (OP: 1.4+/-0.7, CPB: 2.5+/-1.0). The frequency of patients transfused with blood products was significantly (P=0.004) higher in the CPB group (47.3%) than in the OP group (19.5%). The only independent predictors of transfusions, determined by stepwise multivariate logistic regression analysis, was the use of cardiopulmonary bypass (OR: 4.1, CI: 1.6 - 10.1), and female gender (OR: 7.0, CI: 2.1 - 16.1). CONCLUSION: In our centre, off pump coronary surgery is associated with reduced transfusion of blood products.

Multivessel off-pump coronary artery bypass grafting in a nonagenarian: anesthesiologic management.

A 90-year-old male admitted with history of angina (three-vessel disease) on medical therapy for hypertension and chronic renal failure was scheduled for elective coronary artery bypass grafting (CABG). After standard premedication and monitoring anesthesia was induced with propofol and maintained with isoflurane. Middle dose opioids and atracurium were also given. Multivessel revascularization was done through median sternotomy and anastomoses were performed with the aid of coronary stabilization and shunting. Cerebral and renal perfusion were maintained with high arterial pressure (140/70 mmHg) and continuous infusion of fenoldopam (0.05 microg kg(1) m(-1)). The perioperative period was uneventful. Elderly patients are at increased risk for mortality and morbidity after CABG. The procedure can be performed safely on elderly patients without using cardiopulmonary bypass and preventing cerebral and renal ipoperfusion.

Beating-heart coronary artery bypass graft surgery at San Raffaele Hospital: four years of experience.

OBJECTIVE: To review the database of 1,902 consecutive patients who underwent coronary artery bypass graft (CABG) surgery in the period 1998 through 2001 at this institution, and to compare the preoperative status, anesthetic management, and postoperative outcome of 364 patients with the beating-heart technique with 1,538 patients who underwent the operation on cardiopulmonary bypass. DESIGN: Observational study. SETTING: University hospital. PARTICIPANTS: Consecutive patients (n = 1,902) who underwent CABG surgery in the period 1998 through 2001. MEASUREMENTS AND MAIN RESULTS: Comparison (chi-square test) of the preoperative status shows that surgeons' choice for the beating-heart technique was based on the presence of severe preoperative comorbidities: renal impairment (p < 0.0001), chronic obstructive pulmonary disease (p < 0.04), and low ejection fraction (p < 0.0001). On a multivariate analysis, the beating-heart technique was associated with reduced transfusion needs and duration of mechanical ventilation. CONCLUSION: Beating-heart surgery is gaining popularity as a safe method for myocardial revascularization. Excellent results have been achieved with this technique in this center.

Activation of coagulation and fibrinolysis during coronary surgery: on-pump versus off-pump techniques.

BACKGROUND: The authors studied the changes in selected hemostatic variables in patients undergoing coronary surgery with on-pump coronary artery bypass grafting (CABG) or off-pump coronary artery bypass surgery (OPCAB) techniques. METHODS: Platelet counts and plasma concentrations of antithrombin, fibrinogen, D dimer, alpha(2) antiplasmin, and plasminogen were measured preoperatively, 5 min after administration of heparin, 10 min after arrival in the intensive care unit, and 24 h after surgery in patients scheduled to undergo OPCAB (n = 15) or CABG (n = 15). To correct for dilution, hemostatic variables and platelet counts were adjusted for the changes in immunoglobulin G plasma concentrations and hematocrit, respectively. RESULTS: Adjusting for dilution, antithrombin and fibrinogen concentrations decreased to a similar extent in patients undergoing OPCAB or CABG (pooled means and 95% confidence limits of the mean: 95.5% of baseline, 93-98%, P = 0.002, and 91.7% of baseline, 88-95%, P = 0.0001), respectively, whereas alpha(2)-antiplasmin concentrations were unchanged. Only CABG was associated with a reduction in platelet counts (76% of baseline, 66-85%, P = 0.0001), plasminogen concentrations (96% of baseline, 91-99%, P = 0.011), and increased D-dimer formation (476%, 309-741%, P = 0.004). Twenty-four hours after surgery, platelet counts were still lower in patients undergoing CABG (P = 0.049), but all the investigated variables adjusted for dilution were similar in the two groups. CONCLUSIONS: Coronary surgery causes a net consumption of antithrombin and fibrinogen. A transient decrease in platelet counts, with plasminogen activation and increased D-dimer formation, however, is only observed with CABG. Twenty-four hours after surgery, the hemostatic profiles of patients in both groups are similar.

Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study.

BACKGROUND: We evaluated the hemostatic effects of tranexamic acid, a synthetic antifibrinolytic drug, in patients undergoing beating-heart coronary surgery. METHODS: Forty consecutive patients were in a double-blind manner, prospectively randomized into two groups: 20 patients received tranexamic acid (bolus of 1 g before skin incision, followed by continuous infusion of 400 mg/hr during surgery), and 20 patients received saline. As primary outcomes, bleeding and allogeneic transfusions were considered. D-dimer and fibrinogen plasma levels were also evaluated to monitor the activation of fibrinolysis. Major postoperative thrombotic events, as a potential consequence of antifibrinolytic treatment, were recorded. RESULTS: The treatment group had significantly lower postoperative bleeding (median [25th to 75th percentiles]: 400 mL [337 to 490 mL] vs 650 ml [550 to 862 mL], p < 0.0001), lower need for allogeneic blood products (1,200 vs 5,300 mL, p < 0.001), and lower postoperative D-dimer plasma levels. No postoperative thrombotic complications were observed in either group. CONCLUSIONS: In this initial series of patients undergoing off-pump coronary surgery, tranexamic acid appears to be effective in reducing postoperative bleeding and the need for allogeneic blood products.

Tranexamic acid administration after cardiac surgery: a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: Many different doses and administration schemes have been proposed for the use of the antifibrinolytic drug tranexamic acid during cardiac surgery. This study evaluated the effects of the treatment using tranexamic acid during the intraoperative period only and compared the results with the effects of the treatment continued into the postoperative period. METHODS: Patients undergoing elective cardiac surgery with use of cardiopulmonary bypass (N = 510) were treated intraoperatively with tranexamic acid and then were randomized in a double-blind fashion to one of three postoperative treatment groups: group A: 169 patients, infusion of saline for 12 h; group B: 171 patients, infusion of tranexamic acid, 1 mg x kg(-1) x h(-1) for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg x kg(-1) x h(-1) for 12 h. Bleeding was considered to be a primary outcome variable. Hematologic data, allogeneic transfusions, thrombotic complications, intubation time, and intensive care unit and hospital stay duration also were evaluated. RESULTS: No differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg x kg(-1) x h(-1) tranexamic acid required more units of packed red blood cells because of a significantly lower basal value of hematocrit, as shown by multivariate analysis. CONCLUSIONS: Prolongation of treatment with tranexamic acid after cardiac surgery is not advantageous with respect to intraoperative administration alone in reducing bleeding and number of allogeneic transfusions. Although the prevalence of postoperative complications was similar among groups, there is an increased risk of procoagulant response because of antifibrinolytic treatment. Therefore, the use of tranexamic acid during the postoperative period should be limited to patients with excessive bleeding as a result of primary fibrinolysis.

Tranexamic acid compared with high-dose aprotinin in primary elective heart operations: effects on perioperative bleeding and allogeneic transfusions.

OBJECTIVE: Since excessive fibrinolysis during cardiac surgery is frequently associated with abnormal perioperative bleeding, many authors have advocated prophylactic use of antifibrinolytic drugs to prevent hemorrhagic disorders. We compared the effects of tranexamic acid (a synthetic antifibrinolytic drug) with aprotinin (a natural derivative product with antifibrinolytic properties) on perioperative bleeding and the need for allogeneic transfusions. METHODS: In a single-center prospective randomized unblinded trial, 1040 consecutive patients undergoing primary, elective cardiac operations with cardiopulmonary bypass received either high-dose aprotinin or tranexamic acid. The aprotinin group (518 patients) received 280 mg in 20 minutes before the skin incision, 280 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 70 mg/h throughout the operation. The tranexamic acid group (522 patients) received 1 g in 20 minutes before the skin incision, 500 mg in the priming solution of the extracorporeal circuit, and a continuous infusion of 400 mg/h during the operation. Postoperative bleeding, perioperative transfusions, and hematologic variables were evaluated at fixed times. Postoperative thrombotic complications, intubation time, intensive care unit stay, and hospital stay were recorded. RESULTS: Postoperative bleeding was similar in the 2 groups: aprotinin 250 mL (150-400 mL) versus tranexamic acid 300 mL (200-450 mL) (median and 25th-75th quartiles), median difference of 50 mL (95% confidence intervals, 0-50 mL). The number of transfusions and the outcome did not differ. CONCLUSIONS: Tranexamic acid and aprotinin show similar clinical effects on bleeding and allogeneic transfusion in patients undergoing primary elective heart operations. Since tranexamic acid is about 100 times cheaper than aprotinin, its use is preferable in this type of patient.

[The effectiveness of enoximone in patients with serious left ventricular dysfunction submitted for aorto-coronary bypass]. / Efficacia dell'enoximone in pazienti con grave disfunzione ventricolare sinistra sottoposti a bypass aorto-coronarico.

BACKGROUND: The purpose of this study was to investigate whether the combined positive inotropic and vasodilating properties of enoximone have a short-term benefit when used in patients who underwent open heart surgery. METHODS: From 7/1994 to 1/1995 twenty-six patients with severe myocardial dysfunction (ejection fraction < 35%) were enrolled into a prospective trial before undergoing coronary artery bypass graft. They were randomly selected into two study groups: the first treated with enoximone (group E) and the other one with dopamine (group D). Anaesthesia was the same for both groups using high-dose fentanyl. Buckberg cardioplegia was used. All patients were followed by: conventional monitoring, Swan-Ganz catheter and transesophageal echocardiography. measurements (hemodynamic parameters, end-systolic and diastolic area and left ventricular wall motion) were recorded: after induction of anesthesia, after loading-dose and an intensive care unit. Enoximone- and dopamine infusions were started during weaning from cardiopulmonary bypass and tailored to hemodynamic parameters (cardiac index > 2.8 l/min, wedge pressure < 16 mmHg, mixed venous blood saturation > 65%). Major events were defined as: endotracheal intubation > 36 h, using intraortic balloon pump or centrifugal pump, intensive care timer > 48 h, in hospital cardiac death. Prices, were established by DRG-tables (diagnosis related groups). Statistical analysis were performed by X and "t" Student tests. RESULTS: Cardiac index increased more significantly in group E (CI 1.9-->3.9 vs 2.3-->3.3; p 0.05) thanks to a higher reduction of vascular systemic (SVRI 2889-->1447 vs 2536 -->1565; p 0.005) and pulmonary resistances (PVRI 271-->193 vs 288-->218; p 0.05). Fewer major cumulative events and intensive care costs were observed in group E rather than group D. CONCLUSIONS: Enoximone administer immediately after open heart surgery had more beneficial hemodynamic and clinical effects than dopamine in patients with severe left ventricular dysfunction.

[Diastolic dysfunction in cardiac surgery intensive care. Study methods, changes and prognosis]. / La disfunzione diastolica in terapia intensiva cardiochirurgica. Modalità di studio, evoluzione e prognosi.

The natural history of patients with coronary artery disease and diastolic dysfunction who underwent coronary artery bypass grafting (CABG) is not well known. The aims of our study were to evaluate the incidence of diastolic dysfunction, its evolution after CABG and its possible correlation with adverse in-ICU prognosis. We studied 88 consecutive patients scheduled for CABG with not severely depressed left ventricular function (ejection fraction > 35%) and multivessels disease. Buckberg cardioplegia was used for myocardial protection. Diastolic function was investigated by recording mitral and venous pulmonary flow by transesophageal Doppler echocardiography (TEE). TEE examination was performed in operative room pre and post-bypass, at ICU arrival and after three months. Diastolic dysfunction was defined as mild, moderate and severe. Adverse in ICU events were defined as: use of inotropic drugs or ventricular mechanical support, an ICU stay > 24 hours, perioperative myocardial infarction and death. The study group was compared with a control group. T-Student test was used; a p < 0.05 was considered significant. A reduced diastolic function was present in 77% of patients at baseline examination. Diastolic dysfunction did not worsen significantly after hypothermic cardiac arrest and reperfusion. It persisted during ICU stay and normalized after three months from CABG in the majority of patients (85%). Diastolic failure was not associated with an adverse ICU prognosis (adverse events: 18 versus 13%; p = ns).