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.

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).

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet-based process with a final meeting on 28 June 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, the use of pre-operative intra-aortic balloon counterpulsation, and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic ß-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference.

BACKGROUND: There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first international consensus conference on this topic. METHODS: The consensus was a continuous international internet-based process with a final meeting on June 28th 2010 in Milan at the Vita-Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting and ranking. RESULTS: Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, the use of preoperative intra-aortic balloon counterpulsation and referral to high-volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. CONCLUSION: This international consensus conference has identified the non-surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra-aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic beta-blockade, early aspirin therapy, and referral to high-volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

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.

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.

Right ventricular failure: physiology and assessment.

Right ventricular function can be altered in several disease states involving lungs and heart. Severe right ventricular dysfunction is a major determinant of outcome in such situations, and may strongly influence clinical management. The complex geometry of the right ventricle and the different physiology with respect to the left ventricle make the right ventricular failure difficult to define and assess. The response to increased afterload is the main determinant of right ventricle physiology in pathologic conditions. This consists of right ventricular hypertrophy and enlargement, with reduced coronary blood flow to the right ventricular wall, dilation of tricuspid annulus and displacement of interventricular septum. This latter change involves the left ventricular diastolic function, which is reduced by leftward septal shifting. In right ventricle myocardial ischemia and infarction the primum movens of altered right ventricular function is not an increase in afterload, but the ischemic involvement of the right ventricle, more often in the setting of an inferior acute myocardial infarction. The assessment of right ventricular failure is based on thermodilution by pulmonary artery catheter, contrast and radionuclide ventriculography, echocardiography, and magnetic resonance. Among these techniques, thermodilution and echocardiography play a relevant role in clinical scenarios, being readily available and feasible bedside.

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.

Upper extremity surgical treatment of cerebral palsy.

The purpose of this report is to review the surgical treatment of the upper extremity involved with cerebral palsy over a 25-year period and present our results with regard to changes in upper limb function. Surgical results were assessed by comparison of preoperative and postoperative levels of upper extremity functional use using a previously described 9-level scale. The effect of the following cofactors on surgical outcome were examined: type of cerebral palsy, age, voluntary control, mental impairment, sensibility, and type of surgical treatment. One hundred eighty operations representing 718 procedures in 134 patients were reviewed. Surgical treatment was based on the following principles: soft tissue releases of deforming spastic muscles, tendon transfers to augment antagonistic activity, and joint stabilization. Surgical planning was tailored to each child's particular needs. Comparison of the preoperative and postoperative 9-level functional use scores showed an average improvement of 2.6 functional levels for all patients. Patients with fair and good voluntary control had significantly greater improvement in functional use scores than those with poor voluntary control. No other statistically significant predictive cofactor was found. In selected patients with upper extremity dysfunction secondary to spastic cerebral palsy, surgical intervention improves function, as measured by the upper extremity functional use scale.