A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Methylene Blue Reduces Mortality in Critically Ill and Perioperative Patients: A Meta-Analysis of Randomized Trials.

Vasodilatory hypotension is common in critically ill and perioperative patients, and is associated with adverse outcomes. As a nitric oxide production inhibitor, methylene blue (MB) exerts its vasoconstrictor property and is an adjuvant for catecholamine-refractory vasodilatory shock. However, the effects of MB on clinically relevant outcomes remain unclear. Therefore, the authors performed a meta-analysis of randomized trials on MB in critically ill and perioperative patients. The authors searched through databases for randomized trials on MB in critically ill and perioperative patients, which yielded 11 studies consisting of 556 patients. The primary outcome was mortality at the longest follow-up. Secondary outcomes included hemodynamic parameters and organ dysfunction (PROSPERO: CRD42023409243). Nine out of the 11 included randomized trials reported mortality, which was significantly lower in the MB group (risk ratio, 0.60 [95% CI 0.43-0.84] p = 0.003), with findings confirmed in septic shock and cardiac surgery subgroups. The authors found reduced lengths of stay in the intensive care unit (mean difference [MD], -0.9 days [95% CI -1.06 to -0.77] p < 0.001) and in the hospital (MD, -2.2 days [95% CI, -2.68 to -1.70] p < 0.001) in the MB group. MB was associated with increased mean arterial pressure (MD, 8.4 mmHg [95% CI 5.01-11.75] p < 0.001) and systemic vascular resistance (MD, 94.5 dyn/s/cm5 [95% CI 17.73-171.15] p = 0.02), with no difference in cardiac output (standardized MD, 0.16 [95% CI, -0.25 to 0.57] p = 0.45). This meta-analysis showed that MB reverses vasodilation in critically ill and perioperative patients and might improve survival. Further adequately powered randomized trials are needed to confirm these findings.

Remimazolam for anesthesia and sedation in pediatric patients: a scoping review.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism.

Prevention of Cardiac Surgery-Associated Acute Kidney Injury by Implementing the KDIGO Guidelines in High-Risk Patients Identified by Biomarkers: The PrevAKI-Multicenter Randomized Controlled Trial.

BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.

Esmolol in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVE: To assess whether the administration of the ultra-short-acting ß-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. DESIGN: Single-center, double-blinded, parallel-group randomized controlled trial. SETTING: A tertiary care referral center. PARTICIPANTS: Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction <50%. INTERVENTIONS: Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. MEASUREMENTS AND MAIN RESULTS: The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). CONCLUSIONS: In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

A Multinational Observational Study Exploring Adherence With the Kidney Disease: Improving Global Outcomes Recommendations for Prevention of Acute Kidney Injury After Cardiac Surgery.

BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.

Differences in Biomarkers Pattern Between Severe Isolated Right and Left Ventricular Dysfunction After Cardiac Surgery.

OBJECTIVE: To find out if there are any differences in biomarkers between severe isolated right ventricular (RV) dysfunction and severe isolated left ventricular (LV) dysfunction after cardiac surgery using cardiopulmonary bypass. DESIGN: Observational study. SETTING: Teaching hospital. PARTICIPANTS: A total of 46 patients who had severe isolated RV or LV dysfunction after cardiac surgery. INTERVENTION: The authors collected perioperative clinical and biomarker data. MEASUREMENTS AND MAIN RESULTS: Severe isolated RV dysfunction patients (n = 20) had higher postoperative direct bilirubin (p = 0.030), total bilirubin (p = 0.044), glucose (p = 0.011), and international normalized ratio (INR) (p = 0.050) by repeated measure analysis of variance when compared with patients with severe isolated LV dysfunction (n = 26). The RV group also showed lower preoperative alanine transferase (19.3 ± 1.5 v 32.7 ± 4.2, p = 0.001), higher 4-hour INR (1.5 ± 0.3 v 1.4 ± 0.2, p = 0.008), and higher 48-hour INR (1.8 ± 0.4 v 1.4 ± 0.1, p < 0.001). None in the LV group died, whereas 4 patients in the RV group died (all of them had preoperative atrial fibrillation and underwent double valve replacement surgery). CONCLUSION: The authors observed biomarkers differences between severe isolated RV dysfunction and severe isolated RV dysfunction.

Management of Challenging Cardiopulmonary Bypass Separation.

SEPARATION from cardiopulmonary bypass (CPB) after cardiac surgery is a progressive transition from full mechanical circulatory and respiratory support to spontaneous mechanical activity of the lungs and heart. During the separation phase, measurements of cardiac performance with transesophageal echocardiography (TEE) provide the rationale behind the diagnostic and therapeutic decision-making process. In many cases, it is possible to predict a complex separation from CPB, such as when there is known preoperative left or right ventricular dysfunction, bleeding, hypovolemia, vasoplegia, pulmonary hypertension, or owing to technical complications related to the surgery. Prompt diagnosis and therapeutic decisions regarding mechanical or pharmacologic support have to be made within a few minutes. In fact, a complex separation from CPB if not adequately treated leads to a poor outcome in the vast majority of cases. Unfortunately, no specific criteria defining complex separation from CPB and no management guidelines for these patients currently exist. Taking into account the above considerations, the aim of the present review is to describe the most common scenarios associated with a complex CPB separation and to suggest strategies, pharmacologic agents, and para-corporeal mechanical devices that can be adopted to manage patients with complex separation from CPB. The routine management strategies of complex CPB separation of 17 large cardiac centers from 14 countries in 5 continents will also be described.

Preoperative intra-aortic balloon pump to reduce mortality in coronary artery bypass graft: a meta-analysis of randomized controlled trials.

INTRODUCTION: The intra-aortic balloon pump is routinely used in cardiac surgery; however, its impact on outcome is still a matter of debate and several randomized trials have been published recently. We perform an updated meta-analysis of randomized controlled trials that investigated the use of preoperative intra-aortic balloon pump in adult patients undergoing coronary artery bypass grafting. METHODS: Potentially eligible trials were identified by searching the Medline, Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not restricted by language or publication status and were updated in August 2014. Randomized controlled trials on preoperative intra-aortic balloon pump in patients undergoing coronary artery bypass grafting either with or without cardiopulmonary bypass were identified. The primary end point was mortality at the longest follow-up available and the secondary end point was 30-day mortality. RESULTS: The eight included randomized clinical trials enrolled 625 patients (312 to the intra-aortic balloon pump group and 313 to control). The use of intra-aortic balloon pump was associated with a significant reduction in the risk of mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to 0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight studies included). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting 30-day follow-up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. CONCLUSIONS: Preoperative intra-aortic balloon pump reduces perioperative and 30-day mortality in high-risk patients undergoing elective coronary artery bypass grafting.

Primary anticoagulation with bivalirudin for patients with implantable ventricular assist devices.

Bivalirudin is a direct thrombin inhibitor that is increasingly used in patients undergoing mechanical circulatory support as it presents many advantages compared with unfractionated heparin. The aim of this study was to describe our experience with bivalirudin as primary anticoagulant in patients undergoing ventricular assist device (VAD) implantation. An observational study was performed on 12 consecutive patients undergoing VAD implantation at our institution. Patients received a continuous infusion of bivalirudin, with a starting dose of 0.025 mg/kg/h; the target activated partial thromboplastin time (aPTT) was between 45 and 60 s. Patients never received heparin during hospitalization nor had a prior diagnosis of heparin-induced thrombocytopenia (HIT). All patients received a continuous flow pump except one. Preoperative platelets count was 134 000 ± 64 000 platelets/mm(3) . Mean bivalirudin dose was 0.040 ± 0.026 mg/kg/h over the course of therapy (5-12 days). Lowest platelets count during treatment was 73 000 ± 23 000 platelets/mm(3) . No thromboembolic complications occurred. Two episodes of minor bleeding from chest tubes that subsided after reduction or temporary suspension of bivalirudin infusion were observed. Intensive care unit stay was 8 (7-17) days, and hospital stay was 25 (21-33) days. Bivalirudin is a valuable option for anticoagulation in patients with a VAD and can be easily monitored with aPTT. The use of a bivalirudin-based anticoagulation strategy in the early postoperative period may overcome many limitations of heparin and, above all, the risk of HIT, which is higher in patients undergoing VAD implantation. Bivalirudin should no longer be regarded as a second-line therapy for anticoagulation in patients with VAD. [Correction added on 6 December 2013, after first online publication: The dose of bivalirudin in the Abstract to 0.025 mg/kg/h].

Dexmedetomidine reduces the risk of delirium, agitation and confusion in critically Ill patients: a meta-analysis of randomized controlled trials.

OBJECTIVES: Delirium frequently is observed in critically ill patients in the intensive care unit (ICU) and is associated strongly with a poor outcome. Dexmedetomidine seems to reduce time to extubation and ICU stay without detrimental effects on mortality. The objective of the authors' study was to evaluate the effect of this drug on delirium, agitation, and confusion in the ICU setting. DESIGN: Meta-analysis of all the randomized clinical trials ever performed on dexmedetomidine versus any comparator in the ICU setting. SETTING: Intensive care units. PARTICIPANTS: Critically ill patients. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials. Primary endpoint was the rate of delirium, including the adverse events, agitation and confusion. The 13 included manuscripts (14 trials) randomized 3,029 patients. Overall analysis showed that the use of dexmedetomidine was associated with significant reductions in the incidence of delirium, agitation and confusion (298/1,565 [19%] in the dexmedetomidine group v 337/1,464 [23%] in the control group, RR = 0.68 [0.49 to 0.96], p = 0.03). Results were confirmed in subanalyses performed on patients undergoing noninvasive ventilation (1/53 [2%] in the dexmedetomidine group v 7/49 [14%] in the control group, RR=0.18 [0.03 to 1.01], p = 0.05), receiving midazolam as a comparator (268/1,164 [23%] in the dexmedetomidine group v 277/1,025 [27%] in the control group, RR = 0.68 [0.47 to 1.00], p = 0.05) and in general ICU setting patients (204/688 [30%] in the dexmedetomidine group v 204/560 [36%] in the control group, RR = 0.68 [0.45 to 0.81], p < 0.01). CONCLUSIONS: This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce delirium in critically ill patients.

Acute normovolemic hemodilution in cardiac surgery: rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Extracorporeal Membrane Oxygenation for Hemodynamic Support of Ventricular Tachycardia Ablation.

BACKGROUND: We report the experience in a cohort of consecutive patients receiving extracorporeal membrane oxygenation during catheter ablation of unstable ventricular tachycardia (VT) at our center. METHODS AND RESULTS: From 2010 to 2015, extracorporeal membrane oxygenation was initiated in 64 patients (average age: 63±15 years; left ventricular ejection fraction in 27±9%; cardiogenic shock in 23%, and electrical storm in 62% of patients) undergoing 74 unstable VT catheter ablation procedures. At least one VT was terminated in 81% of procedures with baseline inducible VT, and VT noninducibility was achieved in 69%. Acute heart failure occurred in 5 patients: 3 underwent emergency heart transplantation, 1 had left ventricular assist device (LVAD) implantation, and 1 patient eventually died because of subsequent mesenteric ischemia. All other patients were discharged alive. After a median follow-up of 21 months (13-28 months), VT recurrence was 33%; overall survival was 56 out of 64 patients (88%). Extracorporeal membrane oxygenation-supported ablation was the bridge to LVAD in 6.9% and to heart transplantation in 3.5% of patients. VT recurrence was related to ablation success (after 180 days of follow up: 19% when VT was noninducible, 42% if nonclinical VT was inducible, 75% when clinical VT was inducible, and 75% in untested patients, P<0.001). Incidence of all-cause death, heart transplantation, and LVAD was independently related to ablation outcome (at 180 days of follow-up: 9% when noninducibility was achieved, 50% in case of inducible VT, and 75% in untested patients, P<0.001). At multivariable analyses, noninducibility (hazard ratio 0.198; P=0.001) and left ventricular ejection fraction (hazard ratio 0.916; P=0.008) correlated with all-cause death, LVAD, and heart transplantation. CONCLUSIONS: Ablation of unstable VTs can be safely supported by extracorporeal membrane oxygenation, which allows rhythm stabilization with low procedure mortality, bridging decompensated patients to permanent LVAD or heart transplantation. Successful ablation is associated with better outcomes than unsuccessful ablation.

Urinary neutrophil gelatinase-associated lipocalin time course during cardiac surgery.

BACKGROUND: NGAL is one of the most promising AKI biomarkers in cardiac surgery. However, the best timing to dose it and the reference values are still matter of discussion. AIM OF THE STUDY: We performed a uNGAL perioperative time course, to better understand its perioperative kinetics and its role in AKI diagnosis. SETTING OF THE STUDY: San Raffaele University Hospital, cardiac surgery department. MATERIAL AND METHODS: We enrolled in this prospective observational study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Based on preoperative characteristics, they were divided in low-risk and high-risk patients. uNGAL measurements were collected at pre-defined times before, during, and up to 24 hours after surgery. STATISTICAL ANALYSIS: Data were analysed by use of SAS 1999-2001 program or IBM SPSS Statistics. RESULTS: In low-risk patients, uNGAL had the highest value immediately after general anesthesia induction (basal dosage: uNGAL: 12.20ng×ml -1 , IQR 14.00). It later decreased significantly (3.40 ng×ml -1 , IQR 4.80; P = 0.006) during CPB, and finally return to its original value 24 hours after surgery. In high-risk patients, uNGAL increased immediately after surgery; it had the highest value on ICU arrival (38,20 ng×ml -1 ; IQR 133,10) and remained high for several hours. A difference in uNGAL levels between the two groups was already observed at the end of surgery, but it became statistically significant on ICU arrival (P = 0.002). CONCLUSION: This study helps to better understand the different kinetics of this new biomarker in low-risk and high-risk cardiac patients.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials.

INTRODUCTION: Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. METHODS: Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. RESULTS: We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

Intermittent levosimendan improves mid-term survival in chronic heart failure patients: meta-analysis of randomised trials.

AIMS: Standard inotropic treatment is often necessary in end-stage heart failure but may be harmful. We performed a meta-analysis of randomized controlled trials to investigate the effect of repeated administration of levosimendan on survival in patients with chronic heart failure. METHODS AND RESULTS: Four investigators independently searched in CENTRAL, Google Scholar MEDLINE/PubMed, Scopus and the Cochrane Central Register of clinical trials to identify any randomized study ever performed with intermittent levosimendan intravenous administration in adult patients with chronic heart failure with no restrictions on dose or time of administration. Data from a total of 326 patients from six randomized controlled studies using intermittent levosimendan in a cardiological setting were included in the analysis. Levosimendan was associated with a significant reduction in mortality at the longest follow-up available [32 of 168 (19 %) in the levosimendan group 46 of 133 (35 %) in the control arm, RR = 0.55 (95 % CI 0.37-0.84), p for effect = 0 0.005, p for heterogeneity = 0.3, I (2) = 23.4 %, NNT = 6 with 5 studies included]. Brain natriuretic peptide values, ejection fraction and number of patients with New York Heart Association ≥ III status were similar in survivors of both groups. CONCLUSIONS: A large randomized trial is necessary to confirm the promising beneficial effects of intermittent levosimendan administration on the mid-term survival of patients with chronic heart failure.