Repeated or intermittent levosimendan treatment in advanced heart failure: An updated meta-analysis.

Abstract Introduction Advanced heart failure is a malignant disease characterized by a debilitating late course, with increasingly frequent hospitalisations and high rate of mortality. Levosimendan, an inodilator developed for the treatment of acutely decompensated chronic heart failure, has been recently proposed also as a repetitive treatment of advanced heart failure. Several studies on the use of levosimendan in this settings report mortality data. Independent meta-analyses on the effect on mortality of repetitive or intermittent levosimendan administration in advanced heart failure has been published but were criticized in regard to the selection of the studies. Meanwhile new data became available. We therefore updated the selection of studies and re-analyzed all the available data. Methods & results Data from seven randomized trial and a total of 438 adult patients using intermittent levosimendan in a cardiological setting were included in the present analysis. The average follow-up period was 8±3.8months. The use of levosimendan was associated with a significant reduction in mortality at the longest follow-up available [41 of 257 (16%) in the levosimendan group vs. 39 of 181 (21.5%) in the control arm, OR=0.54 (95% CI 0.32–0.91), p for effect=0.02, p for heterogeneity=0.64, I2=0%]. Conclusions The updated results suggest that repetitive or intermittent levosimendan administration in advanced heart failure is associated with a significant reduction in mortality at the longest follow-up available. There is therefore a strong rationale for a randomized clinical trial with adequate power on mortality

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

Urinary neutrophil gelatinase-associated lipocalin as an early predictor of prolonged intensive care unit stay after cardiac surgery.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein of lipocalin family highly expressed in various pathologic states and is an early biomarker of acute kidney injury in cardiac surgery. We performed an observational study to evaluate the role of NGAL in predicting postoperative intensive care stay in high-risk patients undergoing cardiac surgery. We enrolled 27 consecutive patients who underwent high-risk cardiac surgery with cardiopulmonary bypass. Urinary NGAL (uNGAL) was measured before surgery, at intensive care unit (ICU) arrival and 24 h later. Univariate and multivariate predictors of ICU stay were performed. uNGAL was 18.0 (8.7–28.1) ng/mL at baseline, 10.7 (4.35–36.0) ng/mL at ICU arrival and 29.6 (9.65–29.5) 24 h later. The predictors of prolonged ICU stay at the multivariate analysis were body mass index (BMI), uNGAL 24 h after surgery, and aortic cross-clamp time. The predictors of high uNGAL levels 24 h after at a multivariate analysis were preoperative uNGAL and logistic European System for Cardiac Operative Risk Evaluation. At a multivariate analysis the only independent predictors of prolonged ICU stay were BMI, uNGAL 24 h after surgery and aortic cross-clamp time

Non-adrenergic vasopressors in patients with or at risk for vasodilatory shock. A systematic review and meta-analysis of randomized trials

Introduction: Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality. Methods: PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, nonhuman studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available. Results: A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95%confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction inmortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias. Conclusions: Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians’ opinions and routine practices to understand the clinicians’ response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to “do you agree” and “do you use”) showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location

Effect of Levosimendan Treatment in Pediatric Patients With Cardiac Dysfunction: An Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. Currently, there is only limited evidence that this drug positively affects outcomes. The authors' aim was to investigate the effects of levosimendan on hemodynamic parameters and outcomes in pediatric patients in all clinical settings. The study design was a systematic review of randomized and nonrandomized studies. Randomized clinical trials (RCTs) were included in a meta-analysis. The primary outcome of the meta-analysis was the effect of levosimendan on central venous oxygen saturation (ScvO) and lactate values as surrogate markers of low-cardiac-output syndrome. The study setting was any acute care setting. Study participants were pediatric patients (age <18 years) receiving levosimendan, and the intervention was levosimendan versus any control treatment. The authors identified 44 studies published from 2004 to 2020, including a total of 1,131 pediatric patients. Nine studies (enrolling 547 patients) were RCTs, all performed in a pediatric cardiac surgery setting. Three RCTs were judged to carry a low risk of bias. In the RCTs, levosimendan administration was associated with a significant improvement of ScvO (p = 0.03) and a trend toward lower postoperative lactate levels (p = 0.08). No differences could be found for secondary outcomes. Levosimendan use in pediatric patients is not associated with major side effects and may lead to hemodynamic improvement after cardiac surgery. However, its impact on major clinical outcomes remains to be determined. Overall, the quality of evidence for levosimendan use in pediatric patients is low, and further high-quality RCTs are needed

Jugular vs femoral vein for central venous catheterization in pediatric cardiac surgery (PRECiSE): study protocol for a randomized controlled trial

Abstract Background Placement of central venous catheters (CVCs) is essential and routine practice in the management of children with congenital heart disease. The purpose of the present protocol is to evaluate the risk for infectious complications in terms of catheter colonization, catheter line–associated bloodstream infections, and catheter-related bloodstream infections (CRBSIs), and the mechanical complications from different central venous access sites in infants and newborns undergoing cardiac surgery. Methods One hundred sixty patients under 1 year of age and scheduled for cardiac surgery will be included in this randomized controlled trial (RCT); patients will be randomly allocated to the jugular or femoral vein arms. CVC insertion will be performed by one of three selected expert operators. Discussion The choice of the insertion site for central venous catheterization can influence the incidence and type of infectious complications in adults but this is not unanimously evidenced in the pediatric setting. The experimental hypothesis of this RCT is that the jugular insertion site is less likely to induce catheter colonization and CRBSI than the femoral site. Trial registration ClinicalTrials.gov Identifier: NCT03282292. Registered on 12 September 2017

Additional file 1: of Jugular vs femoral vein for central venous catheterization in pediatric cardiac surgery (PRECiSE): study protocol for a randomized controlled trial

Standard Protocol Items: Recommendation for Interventional Trials (SPIRIT) 2013 Checklist. (PDF 69 kb

Publication trends in the journal of cardiothoracic and vascular anesthesia: A 10-year analysis

Objective Good quality clinical research in anesthesiology is now performed all over the world. The aim of this article was to present and analyze the scientific contributions published in the Journal of Cardiothoracic and Vascular Anesthesia and to give a structured view focused on the countries where these studies were performed. Design Bibliometric analysis. Setting Teaching hospital. Participants None. Interventions The authors analyzed the geographic distribution of the authors publishing in cardiac anesthesia. Measurements and Main Results Data were obtained from the Scopus database. All works belonging to document-type articles, reviews, letters, and editorials published over a 10-year period (2000-2009) in the Journal of Cardiothoracic and Vascular Anesthesia (JCVA) were tracked. For each article, the country of origin of the corresponding author was retrieved. JCVA published 1,816 articles from 45 different countries. The United States accounted for 43.8% of the total, followed by India (8.3%), Germany (5.5%), United Kingdom (4.7%), and Italy (4.4%). Conclusions JCVA has a widespread influence and receives contributions from all over the world. More and more biomedical research is conducted outside North America and Europe, with India leading the group of "rest of the world" countries. The recent development of Asian countries clearly challenges North America and European countries that can no longer ignore the scientific contribution from these parts of the world. With this in mind, some journals such as JCVA are giving voice to these prolific countries, which represents a fundamental forum for these newcomers to the field of cardiac anesthesia. © 2010 Elsevier Inc