Chiara Gerli

Reducing Mortality in Cardiac Surgery With Levosimendan: A Meta-analysis of Randomized Controlled Trials

OBJECTIVES The authors performed a meta-analysis to evaluate whether levosimendan is associated with improved survival in patients undergoing cardiac surgery. DESIGN A meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 440 patients from 10 randomized controlled studies were included in the analysis. INTERVENTIONS None. MEASURMENTS AND MAIN RESULTS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, comparison of levosimendan versus control, and cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no mortality data. The primary endpoint was postoperative mortality. Levosimendan was associated with a significant reduction in postoperative mortality (11/235 [4.7%] in the levosimendan group v 26/205 [12.7%] in the control arm, odds ratio = 0.35 [0.18-0.71], p for effect = 0.003, p for heterogeneity = 0.22, I(2) = 27.4% with 440 patients included), cardiac troponin release, and atrial fibrillation. No difference was found in terms of myocardial infarction, acute renal failure, time on mechanical ventilation, intensive care unit, and hospital stay. CONCLUSIONS Levosimendan has cardioprotective effects that could result in a reduced postoperative mortality. A large randomized controlled study is warranted in this setting.

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, &agr;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 &agr;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.

Levosimendan Reduces Cardiac Troponin Release After Cardiac Surgery: A Meta-analysis of Randomized Controlled Studies

OBJECTIVES The authors performed a meta-analysis to investigate the effects of levosimendan in cardiac surgery. Inotropic drugs have never shown beneficial effects on outcome in randomized controlled studies, with the possible exception of levosimendan. DESIGN A meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 139 patients from 5 randomized controlled studies were included in the analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, and comparison of levosimendan versus control performed on cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoint was postoperative cardiac troponin release. Levosimendan was associated with a significant reduction in cardiac troponin peak release (weighted mean difference = 2.5 ng/dL [-3.86, -1.14], p = 0.0003) and in time to hospital discharge (weighted mean difference = -1.38 days [-2.78, 0.03], p = 0.05). No other relevant outcome (mortality, myocardial infarction, atrial fibrillation, time on mechanical ventilation, and intensive care unit stay) was improved in those patients receiving levosimendan. CONCLUSIONS Levosimendan has cardioprotective effects, resulting in reduced postoperative cardiac troponin release.

The role of sex on VARC outcomes following transcatheter aortic valve implantation with both Edwards SAPIEN™ and Medtronic CoreValve ReValving System® devices: the Milan registry

AIMS To assess outcomes after transcatheter aortic valve implantation (TAVI) according to sex, with the two available valves and four recognised delivery approaches. METHODS AND RESULTS VARC outcomes are reported according to sex for 305 high-risk patients consecutively treated in our centre, via available access routes utilising the Edwards SAPIEN™/SAPIEN™ XT or the Medtronic CoreValve ReValving System® devices. Three hundred and five patients underwent TAVI: 52.1% male and 47.9% female. Females had a smaller body surface area (1.84±0.16 m² vs. 1.70±0.16 m²; p<0.001) and aortic annulus (24.4±1.6 mm vs. 22.6±1.7 mm; p<0.001) with increased symptoms (NYHA Class III/IV 61.6% vs. 73.6%; p=0.026). Conversely, men had more comorbidities: diabetes mellitus (35.2% vs. 21.9%; p=0.010), chronic kidney disease (41.8% vs. 23.3%; p=0.001), chronic obstructive pulmonary disease (45.3% vs. 30.1%; p=0.006) and previous myocardial infarction (28.3% vs. 14.4%; p=0.003). Thirty-day mortality was 4.7% with no difference between groups. There was a trend for females to develop more major vascular complications (11.9% vs. 19.9%; p=0.058). Notably, females required more blood transfusion (38.4% vs. 50.0%; p=0.041). No differences were observed in device success (92.5%; p=0.667), combined safety endpoint (61.8%; p=0.211) or combined efficacy endpoint (72.0%; p=0.889). CONCLUSIONS Female sex was a predictor of major vascular complications with females requiring more transfusion. No differences were noted amongst patients undergoing TAVI in composite safety and efficacy endpoints according to sex.

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.

BackgroundMany 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. MethodsPatients 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 · kg-1 · h-1 for 12 h; group C: 170 patients, infusion of tranexamic acid, 2 mg · kg-1 · 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. ResultsNo differences were found among groups regarding postoperative bleeding and outcomes; however, the group treated with 1 mg·kg-1·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. ConclusionsProlongation 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.

Anesthetic management of transcatheter aortic valve implantation with transaxillary approach.

OBJECTIVE To describe the anesthetic management of transcatheter aortic valve implantation (TAVI) with the transaxillary approach. DESIGN An observational cohort study. SETTING Two university hospitals. PARTICIPANTS Twenty-two patients with severe aortic stenosis (± regurgitation) at high risk for surgical valve replacement, with contraindications for transfemoral TAVI (81 ± 4.9 years; logistic EuroSCORE, 27% ± 16.9%). INTERVENTION General anesthesia or local anesthesia plus sedation followed by postoperative care. MEASUREMENTS AND MAIN RESULTS Local anesthesia plus sedation and general anesthesia were used in 14 and 8 patients, respectively. Two patients undergoing local anesthesia were monitored with transesophageal echocardiography and supported with noninvasive mask ventilation during the procedure. Main complications included hemodynamic instability requiring inotropes (2 patients), severe postimplant aortic regurgitation requiring immediate second valve-in-valve implantation (1 patient), valve embolization requiring open-valve surgery (1 patient), subclavian artery dissection compromising the flow to a mammary artery graft (1 patient), ascending aortic dissection (1 patient), stroke (2 patients), and atrioventricular block requiring pacemaker implantation (3 patients). Four patients experienced an increased (baseline value × 1.5) postoperative serum creatinine. Five patients required red blood cell tranfusions (2 units). Intensive care unit stay and hospital stay were 6 (4-23) hours and 8 (8-9) days, respectively. All patients were alive 30 days after the procedure. The 6-month mortality was 9%. CONCLUSIONS Transaxillary TAVI is feasible in high-risk patients with aortic stenosis and peripheral vasculopathy. Nevertheless, severe procedural complications are possible, and anesthesiologists should be prepared to assist in the management of these conditions.

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

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.

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).

Anesthetic management of transcatheter aortic valve implantation

Transcatheter aortic valve implantation (TAVI) is an emergent technique for high-risk patients with aortic stenosis. TAVI poses significant challenges about its management because of the procedure itself and the population who undergo the implantation. Two devices are currently available and marketed in Europe and several other technologies are being developed. The retrograde transfemoral approach is the most popular procedure; nevertheless, it may not be feasible in patients with significant aortic or ileo-femoral arterial disease. Alternatives include a transaxillary approach, transapical approach, open surgical access to the retroperitoneal iliac artery and the ascending aorta. A complementary approach using both devices and alternative routes tailored to the anatomy and the comorbidities of the single patient is a main component for the successful implementation of a TAVI program. Anaesthetic strategies vary in different centers. Local anaesthesia or general anaesthesia are both valid alternatives and can be applied according to the patients characteristics and procedural instances. General anaesthesia offers many advantages, mainly regarding the possibility of an early diagnosis and treatment of possible complications through the use of transesophageal echocardiography. However, after the initial experiences, many groups began to employ, routinely, sedation plus local anaesthesia for TAVI, and their procedural and periprocedural success demonstrates that it is feasible. TAVI is burdened with potential important complications: vascular injuries, arrhythmias, renal impairment, neurological complications, cardiac tamponade, prosthesis malpositioning and embolization and left main coronary artery occlusion. The aim of this work is to review the anaesthetic management of TAVI based on the available literature.