Martina Crivellari

Cardiac protection by volatile anaesthetics: A multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

Background and objectives: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. Methods: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate‐based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Results: There was a significant (P < 0.001) difference in the postoperative median (25th‐75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3‐9,5) ng dL−1 when compared to patients receiving desflurane 2,5 (1,1‐5,3) ng dL−1. The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5‐104.8) vs. 36.3 (17.9‐86.6) h ng dL−1 (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q‐wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. Conclusions: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Miniaturized cardiopulmonary bypass improves short-term outcome in cardiac surgery: a meta-analysis of randomized controlled studies

OBJECTIVE To investigate whether the use of miniaturized cardiopulmonary bypass translates into decreased morbidity and mortality in patients having cardiac surgery. METHODS We independently conducted a systematic review and meta-analysis of data pooled from existing trials listed in PubMed and conference proceedings. Sixteen studies were identified, including 1619 patients having cardiac surgery. Inclusion criteria were random allocation to treatment and comparison of a miniaturized cardiopulmonary bypass system versus conventional cardiac surgery. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The end points were the rate of neurologic and myocardial damage and the number of patients transfused. RESULTS Miniaturized cardiopulmonary bypass was associated with significant reductions of neurologic damage (4/548 [0.7%] vs 19/555 [3.4%], odds ratio = 0.30 [0.12-0.73], P = .008), reduction in peak cardiac troponin (weighted mean difference = -0.15 ng/dL [-0.18, -0.11], P < .001), and in the number of transfused patients (55/552 [9.9%] vs 101/563 [17.9%], odds ratio = 0.42 [0.28-0.63], P < .001). No difference in mortality was noted (8/758 [1.0%] vs 14/771 [1.8%], odds ratio = 0.60 [0.26-1.39]). CONCLUSIONS Miniaturized cardiopulmonary bypass has beneficial effects resulting in decreased transfusion rate and cardiac and neurologic damage.

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).

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

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.

Human protein C concentrates in adult septic patients

Some case reports and case series suggest that protein C concentrates may improve the outcome in patients with congenital or acquired protein C deficiency (not only in those with sepsis induced purpura fulminans). We reviewed the published literature on the use of protein C concentrates in adult septic patients and found that it is limited to less than 70 patients reported in observational studies with a 70% survival, and added our personal experience (two adult patients with sepsis and contraindications to recombinant activated protein C).

The effect of concomitant radiofrequency ablation and surgical technique (repair versus replacement) on release of cardiac biomarkers during mitral valve surgery.

All patients undergoing heart surgery experience a certain amount of nonspecific myocardial injury documented by the release of cardiac biomarkers and associated with poor outcome. We investigated the role of unipolar radiofrequency ablation of atrial fibrillation on the release of cardiac biomarkers in 71 patients undergoing mitral valve surgery and concomitant left atrial ablation case-matched with 71 patients undergoing isolated mitral surgery. The study was powered to detect a 3 ng/mL difference. There was no difference between the 2 groups in terms of cardiac troponin I (10 ± 5.3 versus 12 + 10.4 ng/mL; P = 0.7) or creatine kinase-MB (50 ± 21.8 versus 57 ± 62.0 ng/mL; P = 0.5) release. Postoperative peak cardiac troponin I levels had univariate associations with the duration of cardiopulmonary bypass (P = 0.002) and aortic cross-clamping (P = 0.001) and with the surgical technique (15 ± 12 ng/mL for mitral valve replacement versus 9 ± 4.8 for mitral valve repair; P = 0.0007) at univariate analysis. Mitral valve replacement was the only independent predictor of postoperative peak release of cardiac troponin I identified with multivariate analysis (P = 0.005). Radiofrequency ablation of atrial fibrillation does not significantly increase cardiac biomarker release compared with isolated mitral surgery; mitral valve repair is associated with less release of cardiac biomarkers compared with mitral valve replacement.

Bispectral index evaluation of the sedative effect of acupuncture in healthy volunteers.

Objective. To evaluate the sedative effect of acupuncture in healthy volunteers by means of the BIS monitor. Secondary end-points were the evaluation of subjective sedative sensation induced by acupuncture and possible lasting of the sedative effect post needles removal. Methods. We performed a cross-over, single-blinded study on 10 healthy volunteers to evaluate objective and subjective sedative effect of acupuncture compared to sham acupuncture. We recorded heart rate, pulse-oxymetry, BIS at baseline, during a 20-min. stimulation period, and for the following 20 minutes after needles removal. Besides, we asked volunteers to score their subjective state by VAS at baseline, after the stimulation period (20th minute) and 20 minutes after needles removal. Results. BIS values were not significantly different between true and sham acupuncture. A suggestive but not statistically significant difference was evident in VAS score, with true- better than sham acupuncture. There was no difference in the incidence of sleep during the experimental phases, nor in the incidence of insomnia or somnolence in the following 24 hours. HR and SpO2 remained always in a normal range. Conclusions. The sedative effect of true acupuncture was not different from that of sham acupuncture in healthy volunteers. We suggest that acupuncture could have a mild sedative action that can be demonstrated only treating anxious patients and not calm volunteers. In our opinion, the low potency of this technique can be an advantage allowing acupuncture safe application in a wide range of settings.

Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature

Endogenous protein C levels are frequently decreased in septic patients, probably due to increased conversion to activated protein C. Protein C levels inversely correlate with morbidity and mortality of septic patients regardless of age, infecting microorganisms, presence of shock, disseminated intravascular coagulation, degree of hypercoagulation, or severity of illness. Taken together, these considerations suggest a strong correlation between protein C pathways and survival from severe sepsis/septic shock, and reinforce the rationale for the attempts to normalize plasma activity of protein C to improve survival, hamper coagulopathy, and modulate inflammation. We therefore conducted a systematic review of all manuscripts describing protein C concentrates administration in adult and pediatric populations. We identified 28 studies, for a total of 340 patients, 70 of whom died (20.6%). Septic patients were the most represented in this review of case reports and case series. In the majority of these patients sepsis was associated with meningitis, purpura fulminans or disseminated intravascular coagulation. No bleeding complications related to the study drug were reported and most studies underlined normalization of inflammatory markers and of coagulation abnormalities. We conclude that protein C concentrate is an attractive option in septic patients (especially those with meningitis, purpura fulminans, or disseminated intravascular coagulation) and that its cost-benefit ratio must be studied with a large multicenter randomized control trial, possibly including also high risk patients with septic shock and multiple organ failure.

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.

Systolic anterior motion after mitral valve repair: A predictive computational model

OBJECTIVES Systolic anterior motion (SAM) can be an insidious complication after mitral repair. Predicting SAM represents a challenge, even for very experienced mitral valve surgeons. The goal of this pilot work was to illustrate for the first time, a computational software able to calculate and prevent SAM during mitral repair. METHODS Using MATLAB graphical user interface, a clinical software to predict SAM, we tested the performances of the software on 136 patients with degenerative mitral valves undergoing repair with standard techniques. A combination of 6 key echocardiographic parameters was used to calculate the SAM risk score. The discriminative performance of the model was assessed by the area under the receiver-operating characteristic curve. The receiver-operating characteristic was used to divide patients into low, medium and high risk for SAM. Simulation of virtual mitral repair (posterior leaflet resection and mitral ring annuloplasty) was also tested to reduce the risk of SAM. RESULTS The incidence of SAM was 8.1%; 73% were detected as high risk by the software. The area under the receiver-operating characteristic model discriminant performance was 0.87 (95% confidence interval: 0.78-0.95). Simulating a posterior leaflet resection with the leaflet length fixed at 15 mm, the estimated SAM risk was updated, and all patients were then classified at low risk. CONCLUSIONS This software is the first computational model designed to predict SAM during mitral repair to show excellent discrimination. This software has the potential to predict SAM risk preoperatively and, after a virtual step-by-step mitral repair simulation, depending on the technique adopted, to always achieve a low-risk SAM profile.