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

BACKGROUND: 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. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study randomized elective patients with bleeding after cardiac surgery despite pre-treatment with tranexamic acid, to receive placebo (saline solution) or a single administration of desmopressin (0.3 µg/kg in saline solution). The primary endpoint was the number of patients requiring red blood cells transfusion after randomization and during hospital stay. Secondary end points were: blood loss from chest tubes during the first 24 h after study drug administration, hours of mechanical ventilation, intensive care unit stay, and in-hospital mortality. RESULTS: The study was interrupted after inclusion of 67% of the planned patients for futility. The number of patients requiring red blood cells transfusion after randomization was 37/68 (54%) in desmopressin group and 33/67 (49%) in placebo group (P = 0.34) with no difference in blood loss: 575 (interquartile 422-770) ml in desmopressin group and 590 (476-1013) ml in placebo group (P = 0.42), mechanical ventilation, intensive care unit stay or mortality. CONCLUSIONS: This multicenter randomized trial demonstrated that, in patients pre-treated with tranexamic acid, desmopressin should not be expected to improve treatment of patients who experience bleeding after cardiac surgery.

Revised ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management. Implications for preoperative clinical evaluation.

Each year, an increasing number of elderly patients with cardiovascular disease undergoing non-cardiac surgery require careful perioperative management to minimize the perioperative risk. Perioperative cardiovascular complications are the strongest predictors of morbidity and mortality after major non-cardiac surgery. A Joint Task Force of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA) has recently published revised Guidelines on the perioperative cardiovascular management of patients scheduled to undergo non-cardiac surgery, which represent the official position of the ESC and ESA on various aspects of perioperative cardiac care. According to the Guidelines effective perioperative cardiac management includes preoperative risk stratification based on preoperative assessment of functional capacity, type of surgery, cardiac risk factors, and cardiovascular function. The ESC/ESA Guidelines discourage indiscriminate routine preoperative cardiac testing, because it is time- and cost-consuming, resource-limiting, and does not improve perioperative outcome. They rather emphasize the importance of individualized preoperative cardiac evaluation and the cooperation between anesthesiologists and cardiologists. We summarize the relevant changes of the 2014 Guidelines as compared to the previous ones, with particular emphasis on preoperative cardiac testing.

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).

The "Mickey Mouse" aortic root: a peculiar transesophageal echo finding.

In the setting of aortic valve regurgitation, aortic valve incompetence can be caused by several mechanisms. Dilatation of a sinus of Valsalva is one possible cause of severe aortic valve regurgitation. Transesophageal echocardiography provides useful information for planning aortic root surgery by accurately describing the functional anatomy and mechanism of aortic valve dysfunction. The dilatation of a sinus of Valsalva can be easily seen in a two-dimensional short axis view of the aortic valve. When dilatation of the right sinus of Valsalva is present, the transesophageal echo view shows that the aortic root has a peculiar appearance, resembling the profile of Mickey Mouse. We suggest that a typical Mickey Mouse aspect of the aortic root, seen by transesophageal echocardiography, should prompt the recognition of dilatation of the right sinus of Valsalva as a mechanism of aortic valve dysfunction and lead to the appropriate reparative surgical technique.

Transoesophageal echocardiography during coronary artery bypass procedures: impact on surgical planning.

INTRODUCTION: Intraoperative transesophageal echocardiography (iTEE) is widely accepted and routinely used during heart valve surgery. However, the impact of iTEE among patients undergoing coronary artery bypass grafting (CABG) is less well documented. In this study, we aim to define the impact of iTEE in patients undergoing myocardial revascularization for severe coronary artery disease. METHODS: We analyzed clinical data and preoperative and intraoperative echocardiograms of all adults who underwent on pump coronary bypass and iTEE between January 2008 and December 2008. RESULTS: 521 patients (mean age 69±14 years) were studied. New prebypass findings were obtained in 82 (15.7%) patients: in 62 (11.9%) of these patients, this information changed the surgical plan. New postbypass findings were obtained in 8 patients (1.5%) and the surgical plan was altered in 4 patients (0.7%). CONCLUSIONS: Overall new findings were obtained in 90 patients (17.2%) and the surgical plan was altered in 66 patients (12.6%). These data support the routine use of iTEE among patients undergoing surgical myocardial revascularization.

Fenoldopam to prevent renal replacement therapy after cardiac surgery. Design of the FENO-HSR study.

INTRODUCTION: Acute kidney injury requiring renal replacement therapy is a serious complication following cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects. Fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal function. The aim of this paper is to describe the design of the FENO-HSR study, planned to assess the effect of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with acute kidney injury after cardiac surgery. METHODS: We're performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian hospitals. Patients who develop acute renal failure defined as R of RIFLE score following cardiac surgery are randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo. RESULTS: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be: mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creatinine and the rate of acute renal failure (following the RIFLE score). CONCLUSIONS: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients undergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial could provide important insights to improve the management strategy of patients at high risk for postoperative acute kidney injury.

Transesophageal echocardiography in the OR and ICU.

The application of transesophageal echocardiography (TEE) in the perioperative setting has been expanding over the past decades. TEE has become increasingly important in the management of critically ill patients both in the operating room and in the intensive care unit (ICU). TEE is a semi-invasive imaging technique that provides a rapid, real-time, bedside assessment of cardiac function and morphology. It provides information about the anatomy of all cardiac structures and their functional status. A comprehensive exam evaluates both ventricles' morphology, dimensions, and wall motion. It can also detect any anatomical abnormalities and the presence of intracardiac masses or thrombi. Over the last few years, a large number of studies in different ICU and critical care settings and populations have demonstrated the feasibility of TEE in the management of hemodynamic instability. Hemodynamic parameters, such as volumes and pressures, can be obtained via TEE assessment of cardiac performance and may be helpful for diagnosis and treatment. Intraoperative TEE is actually considered an important diagnostic tool in patients scheduled for cardiac surgery as well as in high-risk patients undergoing non-cardiac surgery. All types of hemodynamic impairment can be quickly assessed via TEE, and the management of the echo data can define both the cause and the diagnosis.

Effect of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy.

BACKGROUND: Levosimendan, a novel calcium sensitizer, enhances myocardial contractility without affecting intracellular calcium concentration. It also dilates peripheral arterial vessels by acting on ATP-dependent K(+) channels. Ventriculo-arterial coupling, the relationship between myocardial contractility and the arterial system, describes the efficiency of the cardiovascular system by analysing the relationship between myocardial contractility expressed by ventricular elastance (E(es)) and arterial elastance (E(a)). The aim of this prospective clinical investigation was to evaluate the effects of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy. METHODS: Fifteen patients with stable angina and left ventricular dysfunction underwent elective coronary surgery. Before surgery started, ventriculo-arterial coupling and several variables of cardiovascular performance were assessed by invasive monitoring and transoesophageal echocardiography before and after administration of levosimendan (12 mug/kg bolus) in coronary patients under general anesthesia. RESULTS: The cardiac index and ejection fraction increased significantly [from 1.92 +/- 0.4 to 2.1 +/- 0.4 l/min/m(2) (P = 0.0004) and from 31% +/- 6 to 40% +/- 9 (P = 0.001), respectively], while mean arterial pressure and systemic vascular resistances decreased significantly [from 83 +/- 10 to 72 +/- 5 mmHg (P = 0.0016) and from 997 +/- 341 to 855 +/- 324 dyne s/cm(5) (P = 0.0002), respectively]. After administration of levosimendan, E(a) decreased significantly (from 4.3 +/- 1.8 to 3.2 +/- 1.3 mmHg/ml/m(2), P= 0.005), while E(es) significantly increased (from 2.8 +/- 1.6 to 4.4 +/- 2.3 mmHg/ml/m(2), P= 0.05); as a result, E(a)/E(es) decreased significantly (from 1.76 +/- 1 to 0.83 +/- 0.2, P= 0.002). CONCLUSION: Levosimendan improves ventriculo-arterial coupling and cardiovascular performance in coronary patients with left ventricular dysfunction by enhancing myocardial contractility and reducing arterial elastance.

Target controlled infusion: TCI.

Progress in computing technology has allowed the development of target controlled infusion devices, with drugs delivered to achieve specific predicted target blood drug concentrations. Target controlled infusion (TCI) system has been developed as a standardised infusion system for the administration of opioids, propofol and other anaesthetics by target controlled infusion. A set of pharmacokinetic parameters has been selected using computer simulation of a known infusion scheme. The selected model is incorporated into a computer-compatible infusion pump. Clinical trials with such systems have provided appropriate target concentrations for the administration of target controlled infusion of anaesthetic drugs. The technique of TCI strongly influences the development of intravenous anaesthesia and opens a scenario of new and exciting applications in peri-operative anaesthetic management. The launch of ''Diprifusor'' as the first commercially available TCI system for propofol was the cornerstone of a successful research period within the last decade, which evaluated the pharmacokinetic foundations of computer assisted intravenous drug delivery. Nowadays TCI technology is becoming a part of routine anaesthesia technique for the practitioner rather than a research tool for specialists and those who are enthusiasts of intravenous anaesthesia. Besides clinical application in anaesthesia, target controlled systems will play a significant role as research tools in the evaluation of drug interactions in anaesthesia and in the development of new control techniques for the administration of sedative and analgesic drugs in the peri-operative period.

[Cardiac protection is a clinical evidence]. / La cardioprotezione è un'evidenza clinica.

AIM: Anaesthetics may have protective effect against myocardial ischemia. We aimed to investigate if sevoflurane administration could exert myocardial protection during following coronary occlusion in patients with coronary artery disease. METHODS: a). EXPERIMENTAL DESIGN: prospective, randomized study. b). SETTING: University Hospital, cardiac surgical operative theatre. c). PATIENTS: 42 patients with coronary artery disease, scheduled to undergo coronary surgery. INCLUSION CRITERIA: severe coronary stenosis of anterior descending coronary artery; no collateral flow on angiography; at least two normokinetic segments in the myocardial region supplied by the vessel being bypassed. PATIENTS were randomized to receive (group S) or not (group C) sevoflurane administration for 15 min just before coronary occlusion. d). INTERVENTIONS: Transoesophageal Tissue Doppler echocardiographic examination of myocardial systolic and early diastolic velocities in both groups basally and 60 s after coronary occlusion by the surgeon. e). MEASURES: systolic and early diastolic velocities were registered by Tissue Doppler from a long-axis view of the interventricular septum or the anterior wall of the left ventricle. RESULTS: In group C a significant reduction of systolic and diastolic intramyocardial velocities was found during myocardial ischemia due to coronary occlusion. CONCLUSION: Treatment with sevoflurane before coronary occlusion seem effective in reducing functional myocardial impairment due to ischemia.

[Prevention of mycotic infections in liver transplant recipients: comparison of two chemoprophylactic protocols]. / Prevenzione delle infezioni micotiche nei pazienti sottoposti a trapianto epatico: confronto tra due protocolli di chemioprofilassi.

BACKGROUND: The aim of the study was to compare and evaluate the efficacy of two chemoprophylactic protocols against mycotic infections in a liver transplant recipients population. DESIGN: single-blind, randomized. SETTING: Liver transplant Center of a National Health System teaching hospital. METHODS: Eighty-eight consecutive patients submitted to liver transplantation were enrolled in the study. Immediately before surgery they were randomized to receive sequential treatment with intravenous liposomal amphotericine B + oral itraconazole or intravenous fluconazole + oral itraconazole. Intravenous drugs were administered in the first postoperative week, and oral treatments for the following three weeks. In addition to analyzing the frequency and incidence of colonization, local and disseminated infection of mycotic origin, the causes of death and the possible risk factors for mycotic disease have been examined. RESULTS: Eighty-five patients completed the study. No significative difference was evident in the two groups as regards to single organ and systemic fungal infection rate. Two out of a total of 5 deaths were related to mycotic disease. Pre-transplant fungal colonization, more severe liver disease indicating the transplant procedure and the rejection of the graft were all risk factors for the development of mycotic infection. CONCLUSIONS: The two protocols used in the study showed and equal efficacy in preventing fungal infections in liver transplant recipients.

The use of ACTH and beta-endorphin levels to measure the stress impact and safety of extracorporeal lithotripsy.

The authors measured the plasma levels of beta-endorphin and adrenocorticotropic hormone (ACTH) related to pain in 11 urologic patients who underwent extracorporeal lithotripsy. The study included eight male and three female patients (aged 24 to 65 years) with single kidney stones of less than 20 mm who were treated with the Lithoring Multi-One device. The device delivered 2,000 shock waves from 18 kV to 25 kV, increasing by 1 kV every 250 shock waves. Three patients experienced pain, but only one required intravenous analgesia. The assay of plasmatic ACTH and beta-endorphin is proposed to control the safety and the stress impact of new devices and techniques. In addition, the study demonstrates the medicolegal relevance of such an assay in the evaluation of pain.