ABSTRACT
Background and Objectives: Pulmonary complications are a leading cause of morbidity after cardiac surgery. The aim of this study was to develop models to predict postoperative lung dysfunction and mortality. Materials and Methods: This was a single-center, observational, retrospective study. We retrospectively analyzed the data of 11,285 adult patients who underwent all types of cardiac surgery from 2003 to 2015. We developed logistic predictive models for in-hospital mortality, postoperative pulmonary complications occurring in the intensive care unit, and postoperative non-invasive mechanical ventilation when clinically indicated. Results: In the "preoperative model" predictors for mortality were advanced age (p < 0.001), New York Heart Association (NYHA) class (p < 0.001) and emergent surgery (p = 0.036); predictors for non-invasive mechanical ventilation were advanced age (p < 0.001), low ejection fraction (p = 0.023), higher body mass index (p < 0.001) and preoperative renal failure (p = 0.043); predictors for postoperative pulmonary complications were preoperative chronic obstructive pulmonary disease (p = 0.007), preoperative kidney injury (p < 0.001) and NYHA class (p = 0.033). In the "surgery model" predictors for mortality were intraoperative inotropes (p = 0.003) and intraoperative intra-aortic balloon pump (p < 0.001), which also predicted the incidence of postoperative pulmonary complications. There were no specific variables in the surgery model predicting the use of non-invasive mechanical ventilation. In the "intensive care unit model", predictors for mortality were postoperative kidney injury (p < 0.001), tracheostomy (p < 0.001), inotropes (p = 0.029) and PaO2/FiO2 ratio at discharge (p = 0.028); predictors for non-invasive mechanical ventilation were kidney injury (p < 0.001), inotropes (p < 0.001), blood transfusions (p < 0.001) and PaO2/FiO2 ratio at the discharge (p < 0.001). Conclusions: In this retrospective study, we identified the preoperative, intraoperative and postoperative characteristics associated with mortality and complications following cardiac surgery.
Subject(s)
Cardiac Surgical Procedures , Heart-Assist Devices , Adult , Humans , Retrospective Studies , Cardiac Surgical Procedures/adverse effects , Hospital Mortality , Body Mass Index , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
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 (pâ¯=â¯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]; pâ¯=â¯0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; pâ¯=â¯0.08) and the rate of hospital admission at one year (26/95 v 16/96; pâ¯=â¯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; pâ¯=â¯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.
Subject(s)
Cardiac Surgical Procedures , Propanolamines , Humans , Stroke Volume , Ventricular Function, LeftABSTRACT
BACKGROUND: Organ perfusion is a factor of cardiac output and perfusion pressure. Recent evidence shows that dynamic arterial elastance is a reliable index of the interaction between the left ventricle and the arterial system and, in turn, of left ventricular mechanical efficiency. A practical approach to the assessment of dynamic arterial elastance at the bedside is the ratio between pulse pressure variation and stroke volume variation, which might predict the effect of a fluid challenge on the arterial pressure in patients undergoing cardiac surgery. OBJECTIVE: To evaluate the ability of dynamic arterial elastance, measured by the pressure recording analytical method (PRAM), to predict the response of mean arterial pressure (MAP) to a fluid challenge. DESIGN: Prospective observational study. SETTING: Cardiac surgery patients in a university hospital. PATIENTS: Preload-dependent (pulse pressure variation ≥13%), hypotensive (MAP ≤65âmmHg) patients, without right ventricular dysfunction, at the end of cardiac surgery. INTERVENTIONS: A 250âml fluid challenge infused over 3âmin. MAIN OUTCOME MEASURES: A receiver-operating characteristic curve was generated to test the ability of the baseline (before fluid challenge) dynamic arterial elastance (primary endpoint) and all other haemodynamic variables (secondary endpoint) to predict MAP responsiveness (≥10% increase in MAP) after a fluid challenge. RESULTS: Of 270 patients undergoing cardiac surgery, 97 (35.9%) were preload-dependent, hypotensive and received a fluid challenge. Of these 97 patients, 50 (51%) were MAP responders (≥10% increase in MAP) and 47 (48%) were MAP nonresponders (<10% increase in MAP). Baseline dynamic arterial elastance (meanâ±âSD) had an area under the curve of 0.64â±â0.06 [95% confidence interval (CI), 0.53 to 0.73; Pâ=â0.017]. A dynamic arterial elastance at least 1.07 with a grey zone ranging between 0.9 and 1.5 had 86% sensitivity (95% CI, 73 to 94) and 45% specificity (95% CI, 30 to 60) in predicting MAP increase. CONCLUSION: In a hypotensive preload-dependent cardiac surgery cohort without right ventricular dysfunction, dynamic arterial elastance measured by PRAM can predict pressure response for values greater than 1.5 or less than 0.9.
Subject(s)
Arterial Pressure , Cardiac Surgical Procedures , Blood Pressure , Cardiac Output , Cardiac Surgical Procedures/adverse effects , Fluid Therapy , Hemodynamics , Humans , Prospective Studies , Stroke VolumeABSTRACT
PURPOSE: Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. MATERIALS AND METHODS: Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. RESULTS: We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference -1.8; 95% CI -8.4 to 4.9; Pâ¯=â¯.60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. CONCLUSIONS: Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. STUDY REGISTRATION NUMBER: NCT00994825 (ClinicalTrials.gov).
Subject(s)
Cardiac Output, Low/drug therapy , Simendan/therapeutic use , Age Factors , Cardiac Output, Low/mortality , Cardiotonic Agents/administration & dosage , Cardiotonic Agents/therapeutic use , Cardiovascular Surgical Procedures/adverse effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Postoperative Complications/drug therapy , Postoperative Complications/mortality , Simendan/administration & dosage , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND: Bleeding and transfusions affect mortality in aortic surgery. Although tranexamic acid significantly reduced bleeding in multiple settings, its role in major vascular surgery was never studied. The aim of this study was to determine if tranexamic acid reduces blood loss in open abdominal aortic aneurysm (AAA) surgery. METHODS: A total of 100 patients undergoing elective open AAA repair were randomised to receive tranexamic acid (a loading dose of 500 mg and a continuous infusion of 250 mg h-1) or placebo. The primary outcome was intraoperative blood loss, and the secondary outcomes were the number of patients receiving red blood cells, occurrence of thromboembolic events, and mortality. Data were analysed using the intention-to-treat principle. RESULTS: Fifty patients were randomised into each group. Median (inter-quartile range) intraoperative blood loss was 400 (300-1050) ml in the tranexamic acid group vs 500 (360-1000) ml in the placebo group (P=0.44). Transfusion rate was seven/50 (14%) in the tranexamic group vs 12/50 (24%) in the placebo group (P=0.20). No thrombosis was recorded. In a post hoc analysis, postoperative blood loss was reduced in the tranexamic group both at 4 h (60 [40-80] ml vs 100 [60-140] ml, P<0.001) and 24 h (180 [120-275] vs 275 [190-395] ml, P=0.003) after surgery. At 1 yr, three patients were dead, all in the placebo group (P=0.24) and all after 28 days. CONCLUSIONS: Tranexamic acid did not reduce intraoperative blood loss or blood transfusions in open AAA repair, although it may reduce postoperative blood loss without increasing adverse effects. CLINICAL TRIAL REGISTRATION: NCT02335359.
Subject(s)
Antifibrinolytic Agents/therapeutic use , Aortic Aneurysm/surgery , Blood Loss, Surgical/prevention & control , Cardiac Surgical Procedures/methods , Tranexamic Acid/therapeutic use , Aged , Antifibrinolytic Agents/adverse effects , Aortic Aneurysm/mortality , Blood Loss, Surgical/statistics & numerical data , Blood Transfusion/statistics & numerical data , Cardiac Surgical Procedures/mortality , Double-Blind Method , Erythrocyte Transfusion , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Thromboembolism/epidemiology , Thromboembolism/prevention & control , Tranexamic Acid/adverse effectsABSTRACT
OBJECTIVE: To identify reliable predictors of periprocedural intensive care unit (ICU) admission after transvenous lead extraction (LE) in a high-volume center. DESIGN: Retrospective observational study. SETTING: University tertiary-care hospital. PARTICIPANTS: All patients undergoing LE at San Raffaele Scientific Institute, Milan, Italy, from 2005 to 2015. INTERVENTIONS: LE procedures were performed in the electrophysiology laboratories with a cardiac operating room on standby between the end of the morning surgical case and before the start of the afternoon surgical case. Most procedures were conducted with the patient under procedural sedation and analgesia. After LE, patients were admitted either to the ward or to the ICU. Medical history and intraprocedural data were recorded. MEASUREMENTS AND MAIN RESULTS: Of the 389 procedures performed during the study period, 50 patients (13%) were admitted to the ICU owing to persistent hemodynamic instability or intraoperative complications requiring endotracheal intubation. Complete procedural success was achieved in 370 patients (95%), and the clinical success rate was 98.4%. No deaths were recorded. Five complications requiring emergency surgery (1.3%) were reported. Preprocedural right ventricular dysfunction (odds ratio (OR) 7.41; confidence interval 1.85-29.7; p < 0.01) and the need for general anesthesia (OR 12; confidence interval 1.49-97.06; pâ¯=â¯0.019) were independent predictors of ICU admission. CONCLUSIONS: Preoperative identification of patients who need ICU admission after LE is crucial to increase patient safety and decrease hospital costs. Severe right ventricular dysfunction and need for general anesthesia identify patients with low cardiac reserve who are at increased risk for ICU admission after the procedure.
Subject(s)
Device Removal/adverse effects , Echocardiography, Transesophageal , Intensive Care Units , Pacemaker, Artificial , Aged , Aged, 80 and over , Defibrillators, Implantable , Female , Hospitals, High-Volume , Humans , Male , Middle Aged , Patient Admission , Retrospective StudiesABSTRACT
BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.).
Subject(s)
Anesthesia, Intravenous , Anesthetics, General/pharmacology , Coronary Artery Bypass , Coronary Artery Disease/surgery , Administration, Inhalation , Aged , Anesthesia, General , Anesthetics, Intravenous , Coronary Artery Disease/mortality , Coronary Artery Disease/physiopathology , Elective Surgical Procedures , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mortality , Single-Blind Method , Stroke VolumeABSTRACT
BACKGROUND: Volatile (inhaled) anesthetic agents have cardioprotective effects, which might improve clinical outcomes in patients undergoing coronary-artery bypass grafting (CABG). METHODS: We conducted a pragmatic, multicenter, single-blind, controlled trial at 36 centers in 13 countries. Patients scheduled to undergo elective CABG were randomly assigned to an intraoperative anesthetic regimen that included a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or to total intravenous anesthesia. The primary outcome was death from any cause at 1 year. RESULTS: A total of 5400 patients were randomly assigned: 2709 to the volatile anesthetics group and 2691 to the total intravenous anesthesia group. On-pump CABG was performed in 64% of patients, with a mean duration of cardiopulmonary bypass of 79 minutes. The two groups were similar with respect to demographic and clinical characteristics at baseline, the duration of cardiopulmonary bypass, and the number of grafts. At the time of the second interim analysis, the data and safety monitoring board advised that the trial should be stopped for futility. No significant difference between the groups with respect to deaths from any cause was seen at 1 year (2.8% in the volatile anesthetics group and 3.0% in the total intravenous anesthesia group; relative risk, 0.94; 95% confidence interval [CI], 0.69 to 1.29; P = 0.71), with data available for 5353 patients (99.1%), or at 30 days (1.4% and 1.3%, respectively; relative risk, 1.11; 95% CI, 0.70 to 1.76), with data available for 5398 patients (99.9%). There were no significant differences between the groups in any of the secondary outcomes or in the incidence of prespecified adverse events, including myocardial infarction. CONCLUSIONS: Among patients undergoing elective CABG, anesthesia with a volatile agent did not result in significantly fewer deaths at 1 year than total intravenous anesthesia. (Funded by the Italian Ministry of Health; MYRIAD ClinicalTrials.gov number, NCT02105610.). (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Coronary Artery Bypass , Anesthetics, Inhalation , Anesthesia, General , Anesthesia, IntravenousSubject(s)
Carcinoid Heart Disease/surgery , Cardiac Surgical Procedures/adverse effects , Extracorporeal Membrane Oxygenation/methods , Postoperative Complications/therapy , Ventricular Dysfunction, Right/therapy , Carcinoid Heart Disease/complications , Cardiac Surgical Procedures/methods , Female , Femoral Artery/surgery , Femoral Vein/surgery , Humans , Male , Middle Aged , Postoperative Complications/etiology , Treatment Outcome , Ventricular Dysfunction, Right/etiologyABSTRACT
OBJECTIVE: A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: More than 400 physicians from 52 countries participated in this web-based consensus conference. INTERVENTIONS: The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide. MEASUREMENTS AND MAIN RESULTS: Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions. CONCLUSIONS: This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.
Subject(s)
Cardiac Surgical Procedures/mortality , Cardiac Surgical Procedures/trends , Consensus Development Conferences as Topic , Perioperative Care/methods , Postoperative Complications/mortality , Postoperative Complications/prevention & control , Cardiac Surgical Procedures/adverse effects , Congresses as Topic/trends , Consensus , Humans , Internet/trends , Mortality/trends , Perioperative Care/trends , Randomized Controlled Trials as Topic/methodsABSTRACT
OBJECTIVE:A careful choice of perioperative care strategies is pivotal to improve survival in cardiac surgery. However, there is no general agreement or particular attention to which nonsurgical interventions can reduce mortality in this setting. The authors sought to address this issue with a consensus-based approach.DESIGN:A systematic review of the literature followed by a consensus-based voting process.SETTING:A web-based international consensus conference.PARTICIPANTS:More than 400 physicians from 52 countries participated in this web-based consensus conference.INTERVENTIONS:The authors identified all studies published in peer-reviewed journals that reported on interventions with a statistically significant effect on mortality in the setting of cardiac surgery through a systematic Medline/PubMed search and contacts with experts. These studies were discussed during a consensus meeting and those considered eligible for inclusion in this study were voted on by clinicians worldwide.MEASUREMENTS AND MAIN RESULTS:Eleven interventions finally were selected: 10 were shown to reduce mortality (aspirin, glycemic control, high-volume surgeons, prophylactic intra-aortic balloon pump, levosimendan, leuko-depleted red blood cells transfusion, noninvasive ventilation, tranexamic acid, vacuum-assisted closure, and volatile agents), whereas 1 (aprotinin) increased mortality. A significant difference in the percentages of agreement among different countries and a variable gap between agreement and clinical practice were found for most of the interventions.CONCLUSIONS:This updated consensus process identified 11 nonsurgical interventions with possible survival implications for patients undergoing cardiac surgery. This list of interventions may help cardiac anesthesiologists and intensivists worldwide in their daily clinical practice and can contribute to direct future research in the field.
Subject(s)
Perioperative Period/methods , Perioperative Period/mortalityABSTRACT
BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss. METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE. RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = -0.79; 95% confidence interval [CI], -1.25 to -0.34; P = .001; I = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = -0.64; 95% CI, -0.97 to -0.31; P < .0001; I = 91.8%). CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding.
Subject(s)
Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/trends , Erythrocyte Transfusion/trends , Hemodilution/trends , Postoperative Hemorrhage/therapy , Randomized Controlled Trials as Topic , Cardiac Surgical Procedures/methods , Erythrocyte Transfusion/methods , Hemodilution/methods , Humans , Postoperative Hemorrhage/diagnosis , Postoperative Hemorrhage/etiology , Randomized Controlled Trials as Topic/methods , Transplantation, Homologous/methods , Transplantation, Homologous/trendsABSTRACT
Acute kidney injury (AKI) is one of the most relevant complications after major surgery and is a predictor of mortality. In Western countries, patients at risk of developing AKI are mainly those undergoing cardiovascular surgical procedures. In this category of patients, AKI depends on a multifactorial etiology, including low ejection fraction, use of contrast media, hemodynamic instability, cardiopulmonary bypass, and bleeding. Despite a growing body of literature, the treatment of renal failure remains mainly supportive (e.g. hemodynamic stability, fluid management, and avoidance of further damage); therefore, the management of patients at risk of AKI should aim at prevention of renal damage. Thus, the present narrative review analyzes the pathophysiology underlying AKI (specifically in high-risk patients), the preoperative risk factors that predispose to renal damage, early biomarkers related to AKI, and the strategies employed for perioperative renal protection. The most recent scientific evidence has been considered, and whenever conflicting data were encountered possible suggestions are provided.
ABSTRACT
Although associated with low morbidity and mortality, cardiopulmonary bypass remains a "non-physiologic" device that carries a set of complications. Hepatic and renal impairment are associated with a poor outcome. The knowledge of pathophysiology, risk factors and therapeutic interventions can help the anaesthesiologist in preventing these complications in daily practice. The present narrative review provides an update of the literature on the effects of cardiopulmonary bypass on hepatic and renal functions, focussing on markers of hepatic and renal injuries, perioperative strategies in preserving organ function and replacement therapies.
Subject(s)
Acute Kidney Injury/etiology , Cardiopulmonary Bypass/adverse effects , Liver Diseases/etiology , Postoperative Complications/etiology , Acute Kidney Injury/metabolism , Acute Kidney Injury/prevention & control , Animals , Biomarkers/metabolism , Humans , Liver Diseases/metabolism , Liver Diseases/prevention & control , Postoperative Complications/metabolism , Postoperative Complications/prevention & control , Risk FactorsABSTRACT
PURPOSE: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients. MATERIALS AND METHODS: BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure. RESULTS: Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted. CONCLUSIONS: In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.
Subject(s)
Cardiotonic Agents/therapeutic use , Hydrazones/therapeutic use , Pyridazines/therapeutic use , Sepsis/drug therapy , Dobutamine/therapeutic use , Female , Humans , Male , Middle Aged , Norepinephrine/therapeutic use , Randomized Controlled Trials as Topic , Sepsis/mortality , Shock, Septic/drug therapy , Shock, Septic/mortality , Shock, Septic/therapy , SimendanABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder which is mostly sporadic, although about 5-10% of the cases are inherited. About 15-20% of patients with familial ALS (FALS) carry mutations in the gene encoding the free radical scavenging enzyme Cu/Zn superoxide dismutase (SOD1). In this study, we explored the potential neuroprotective effects of antioxidant strategies based on either a tomato-enriched diet, or pyruvate administration, in an animal model of ALS. To that aim, transgenic mice expressing a mutant form of SOD1 [the gly(93) --> ala (G93A) substitution; G93A SOD1] were fed on either tomato-enriched food pellets or the Altromin diet in which milk serum and proteins substitute for soy and fish flours. In both cases, treatments were started at the 29th day of age. In a second set of experiments, G93A SOD1 mice were treated with pyruvate intraperitoneally (500 mg/kg, i.p; starting at the 70th day of age) and compared with control mice receiving i.p. saline injections. Our results indicate that neither the tomato-enriched diet nor pyruvate administration caused any significant effect on the overall survival time and disease onset in G93A SOD1 mice. Thus, despite the wealth of data indicating the relevant role of oxidative stress and defective energy homeostasis both in patients and animal models of ALS, antioxidant strategies based on tomato-enriched food or pyruvate seem to be not sufficient to promote a disease modifying effect in an animal model of ALS.