Neuroendocrine predictors of vasoplegia after cardiopulmonary bypass.

PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Incidence and treatment of lymphedema in heart transplant patients treated with everolimus.

BACKGROUND: Proliferation signal inhibitors are increasingly used as immunosuppressive drugs in solid organ transplantation. Among their side effects peripheral lymphedema is rarely described in literature. METHODS: All heart transplant patients treated with everolimus (de novo or maintenance) at our center (135 patients: age 50.72±11.1 y, 115 male) were retrospectively analyzed. We considered the incidence of adverse events, particularly the appearance of peripheral edema (13 patients, 9.6%), and the correlation with preoperative characteristics, concomitant medications, other possible causes of edema, as well as all the measures developed for its therapeutic treatment. RESULTS AND CONCLUSIONS: Edema appearance, especially in lower limbs, was considered to be one of the most frequent side effects in heart transplant patients treated with everolimus. In some cases its regression was possible with an adjustment of drug dosages associated with diuretics and lymphatic drainage, but more often a suspension of the drug itself was required for complete regression of the symptoms.

Ex vivo lung perfusion increases the pool of lung grafts: analysis of its potential and real impact on a lung transplant program.

BACKGROUND: Among the strategies to increase the number of lung transplants, ex vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool. METHODS: Data from donors referred to our center were retrospectively analyzed to identify grafts that could potentially be potentially reconditioned by EVLP and for comparison with those obtained by clinical application of EVLP program in our center. RESULTS: Among 75 rejected lungs, 23 organs have been identified as potentially treatable with EVLP with a hypothetic increase of lung transplant activity of 53%. After the introduction of the EVLP program in our center, lung transplantation with reconditioned grafts was performed in 7 (23%) patients with a 30% increase in transplant procedures. CONCLUSION: Although less than expected, EVLP increased the number of lungs suitable for transplantation.

Inhaled nitric oxide versus sodium nitroprusside for preoperative evaluation of pulmonary hypertension in heart transplant candidates.

OBJECTIVE: The development of pulmonary hypertension before heart transplantation increases the risk for postoperative right ventricular failure. Reversibility of pulmonary vascular resistance (PVR), which indicates the feasibility of heart transplantation, can be tested with the use of intravenous vasodilators, such as sodium nitroprusside (NaNTP) or prostacyclin. However, the drawback of these drugs is the development of systemic hypotension. The aim of this study was to evaluate the safely and feasibility of inhaled nitric oxide (iNO) compared with sodium nitroprusside to test PVR reversibility, while avoiding systemic hypotension. MATERIALS AND METHODS: We included all patients who were affected by end stage heart failure undergoing evaluation for heart transplantation if they showed elevated PVR > 2.5 Wood units and mean pulmonary arterial pressure (mPAP) >25 mm Hg. The hemodynamic parameters measured by right heart catheterization were: systolic blood pressure (SBP), mPAP, pulmonary capillary wedge pressure, and cardiac index (CI). The following variables were derived: transpulmonary gradient (TPG) and PVR. All patients were tested by both iNO (20-40 ppm) and intravenous NaNTP, at increasing dosages which were titrated based on systemic pressure. We randomly assigned the order of administration of iNO and NaNTP. RESULTS: The 9 male candidates has an average age of 56 ± 4 years. Seven of the 9 (71%) had postischemic cardiomyopathy, and 2 had idiopathic cardiomyopathy. We observed a reduction of mPAP (32% and 14%), PVR (41% and 32%), TPG (20% and 26%), and SBP (17% and 5%) and an increase of CI with administration of NaNTP and iNO, respectively. CONCLUSIONS: We observed a reduction in PVR and mPAP with administration of either iNO and NaNTP. A better effect of NaNTP was attributed to reducted post-load of the left ventricle. However, the main advantage of iNO was the absence of systemic hypotension and its selectivity for pulmonary vascular system, as underscored by TPG reduction.

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.

The effects of inhaled nitric oxide after lung transplantation.

Primary graft failure (PGF) is one of the major complications that occurs immediately following lung transplantation and greatly contributes to increased morbidity and mortality. The incidence of PGF is correlated with a marked decline in endogenous nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels. Therefore, the administration of NO during lung transplantation has been proposed as a possible therapeutic treatment to prevent or attenuate PGF pathogenesis. Despite the initial positive results of experimental and uncontrolled clinical trials, recent randomized clinical trials do not support the prophylactic administration of inhaled nitric oxide (iNO) for the prevention of PGF following lung transplantation under the conditions tested. Nonetheless, there is evidence that iNO administration during PGF can improve oxygenation and reduce pulmonary hypertension without altering systemic vascular resistance. This suggests that iNO may prevent the need for extracorporeal membrane oxygenation (ECMO) during the hypoxic phase of PGF. During the intraoperative phase of transplantation, one-lung ventilation (OLV) and pulmonary artery clamping usually increase PVR, causing decreased right ventricular function and hemodynamic instability. The administration of iNO during these lung transplant procedures could decrease right ventricular dysfunction by reducing PVR and help to avoid the use of cardiopulmonary bypass.

Clinical experience of anidulafungin for the treatment of patients with documented candidemia.

Candida species are the most common causes of invasive fungal infections in humans, producing infections that range from mucocutaneous disorders to invasive disease that can involve any organ. Here we present our clinical experience with anidulafungin for the treatment of documented nosocomial candidaemia. From february 2009 through January 2010 all patients with documented candidemia treated with anidulafungin in three medical centers in italy were reviewed. Demographics, clinical and microbiological data, and outcome were collected for each patient. Twenty-four patients were included in the study. most patients had a central venous catheter (CVC) or a port-a-cath (100%), had a history of recent surgery (87.5%), or were receiving total parenteral nutrition (79%), broad spectrum antibiotics (83%), steroids or chemotherapy (45.8%). C. albicans (54%) was the most commonly isolated pathogen. CVC was the source of candidemia in 79% of cases. Six patients (25%) developed severe sepsis or septic shock, and five patients had unfavorable outcomes, with an overall mortality rate of 20%. No patients experienced side effects related to anidulafungin therapy. Anidulafungin was effective in the treatment of patients with documented candidemia arising from different sites, and no significant side effects were observed.

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.

Invasive candidiasis and candidemia: new guidelines.

Invasive candidiasis (IC) includes candidemia, disseminated candidiasis with deep organ involvement, endocarditis and meningitis. IC has an attributable mortality of 40% to 50% and is increasingly reported in intensive care units (ICUs). Candida albicans and non-albicans strains are both responsible for infections in ICUs, where empirical and targeted treatments especially need to be initially appropriate. This review synthesizes the most recent guidelines for IC and candidemia from an ICU perspective. Essentially, patients who have been previously exposed to azoles have a higher probability of being infected by azole-resistant or non-albicans strains. Infection site, illness severity, neutropenia, hemodynamic status, organ failure and concomitant drug treatments are host-related factors that influence the choice of anti-fungal treatment. In general, echinocandins are currently favored for empiric treatment of candidemia, especially in critically ill patients or those with previous azole exposure. Pharmacokinetic properties and side effects suggest that polyenes should be avoided in patients with renal failure, and that echinocandins and azoles should be avoided in patients with severe hepatic dysfunction.

Evaluation of adaptive support ventilation in paralysed patients and in a physical lung model.

OBJECTIVE: Evaluation of the respiratory pattern selected by the Adaptive Support Ventilation (ASV) in ventilated patients with acute, chronic respiratory failure and normal lungs and in a physical lung model. DESIGN: We tested ASV both on patients and in a physical lung model, with a normal level of minute ventilation and with minute ventilation increased by 30%. In each patient, respiratory pattern, mechanics and blood gases were recorded. SETTING: General ICU of a University Hospital. RESULTS: In patients with normal lungs, mean values+/-SD were: tidal volume (Vt) 558.1+/-142.4 mL, respiratory rate (RR) 12.6+/-1.3b/min and inspiratory time/total time ratio (Ti/Ttot) 42.4+/-4.1%; in COPD, mean values+/-SD were: Vt 724+/-171 mL, RR 9.2+/-2.7b/min and Ti/Ttot 26.6+/-10.5%; in restrictive ones, mean values+/-SD were: Vt 550.2+/-77.0 mL, RR 15.8+/-2.6b/min, Ti/Ttot 47.5+/-2.5%. In the lung model, at a normal setting, mean values+/-SD were: Vt 523+/-18.5 mL, RR 14+/-0.0b/min, Ti/Ttot 44.0%, in COPD, mean values+/-SD were: Vt 678+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.7%, in restrictive one, mean values+/-SD were: Vt 513+/-12.8 mL, RR 15+/-0.0b/min, Ti/Ttot 48+/-1.5%. In model hyperventilation conditions in a normal setting a Vt of 582+/-16.6 mL, RR 16+/-0.0b/min, Ti/Ttot 48+/-0.0% were selected, in the obstructive setting Vt 883+/-0.0 mL, RR 9+/-0.0b/min, Ti/Ttot 20+/-0.0% and in a restrictive one Vt 545+/-8.4 mL, RR 18+/-0.0b/min, Ti/Ttot 50-0.0%. CONCLUSIONS: In normal patients ASV selected a ventilatory pattern close to the physiological one, in COPD almost a high expiratory time pattern and in restrictive ones a reduced tidal volume pattern. In the model the selection was similar. In the hyperventilation test, ASV chose a balanced increase in both Vt and RR.

[Intra and interindividual variations of pelvic mobility in normal adult walk]. / Variations intra et interindividuelles de la mobilite pelvienne au cours de la marche du sujet sain.

PURPOSE OF THE STUDY: Pelvis motion appears as a main human gait component, it is linked to the lower limb joints and to the spine. Current devices, especially the opto-electronical systems, allow quantitative and tri-dimensional gait studies. The purpose of this study was to quantify the pelvic motion individual variability in a sample of healthy subjects. MATERIALS AND METHODS: The study based on a 18 volunters sample. There were 14 men and 4 women, ranged in age from 25 to 37 years. A clinical examination and a AP radiograph of pelvis allowed to include healthy subjects. We used the three-dimensional analysis VICON system with five cameras. Nine records were performed for each subject during a free-speed walking. These nine records were distributed on three different days. RESULTS: The step length medianes varied from 1100 to 1600 mm with a significantly (p < 0.05) regression between the step length, the walking speed and the subjects height. Vertical pelvic oscillations varied in this sample from 25 to 60 mm and linked with step length and walking speed. Pelvic rotation around the vertical axis varied from 1.5 to 15 degrees. We did not found regression between this pelvic rotation and the length step. It seems there are three types of pelvic rotation around the vertical axis. At the beginning of the stance phase, in type I, the pelvis is in the transversal plane whereas in the type II, it appears with the maximal rotation. In type III, the value of pelvic rotation is very low. The successive lateral inclinations of pelvic described a complex motion which varied from 1.5 to 9 degrees. The rotation of shoulders around the vertical axis varied from 4 degrees to 13 degrees and the successive inclinations varied from 3.25 degrees to 12 degrees. We did not found any regression between the pelvic and shoulders motion values. DISCUSSION: This study showed that the pelvis motion varied considerably from one subject to another. These variations induce different ways of walking with various consequences on the hip joint and the spine. We suppose that these variations could take a part in etiology of some diseases as hip arthritis or in total hip arthroplasty failure, especially in cup wearing.