Giovanni Marino

Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: A prospective, double-blind, randomized clinical trial

Background—Acute renal failure is a serious complication of cardiac surgery causing high morbidity and mortality. The aim of this study was to evaluate the usefulness of fenoldopam, a specific agonist of the dopamine-1 receptor, in patients at high risk of perioperative renal dysfunction. Methods and Results—A prospective single-center, randomized, double-blind trial was performed after local ethical committee approval and after written consent was obtained from 80 patients undergoing cardiac surgery. Patients received either fenoldopam at 0.05 &mgr;g/kg per minute or dopamine at 2.5 &mgr;g/kg per minute after the induction of anesthesia for a 24-hour period. All these patients were at high risk of perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac Surgery Program score >10. Primary end point was defined as 25% creatinine increase from baseline levels after cardiac surgery. The 2 groups (fenoldopam versus dopamine) were homogeneous cohorts, and no difference in outcome was observed. Acute renal failure was similar: 17 of 40 (42.5%) in the fenoldopam group and 16 of 40 (40%) in the dopamine group (P=0.9). Peak postoperative serum creatinine level, intensive care unit and hospital stay, and mortality were also similar in the 2 groups. Conclusions—Despite an increasing number of reports of renal protective properties from fenoldopam, we observed no difference in the clinical outcome compared with dopamine in a high-risk population undergoing cardiac surgery.

Fenoldopam Reduces the Need for Renal Replacement Therapy and In-Hospital Death in Cardiovascular Surgery: A Meta-Analysis

OBJECTIVE Acute renal failure is a common and threatening complication in patients undergoing cardiovascular surgery. To determine the efficacy of fenoldopam in the prevention of acute renal failure, the authors performed a systematic review of randomized, controlled trials and propensity-matched studies in patients undergoing cardiovascular surgery. DESIGN Meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 1,059 patients from 13 randomized and case-matched studies were included in the analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Google Scholar, PubMed, and scientific sessions were searched (updated November 2006). Authors and external experts were contacted. Four unblinded reviewers selected controlled trials that used fenoldopam in the prevention or treatment of acute renal failure in cardiovascular surgery. Four reviewers independently abstracted patient data, treatment characteristics, and outcomes. Pooled estimates showed that fenoldopam consistently and significantly reduced the need for renal replacement therapy (odds ratio = 0.37 [0.23-0.59], p < 0.001) and in-hospital death (odds ratio = 0.46 [0.29-0.75], p = 0.01). These benefits were associated with shorter intensive care unit stay (weighted mean difference [WMD] = -0.93 days [-1.27; -0.58], p = 0.002). Sensitivity analyses, tests for small study bias, and heterogeneity assessment further confirmed the main analysis. CONCLUSIONS This meta-analysis provides evidence that fenoldopam may confer significant benefits in preventing renal replacement therapy and reducing mortality in patients undergoing cardiovascular surgery.

INVASIVE FUNGAL INFECTIONS IN THE INTENSIVE CARE UNIT: A MULTICENTRE, PROSPECTIVE, OBSERVATIONAL STUDY IN ITALY (2006-2008)

Critically ill patients admitted to intensive care units (ICU) are highly susceptible to healthcare‐associated infections caused by fungi. A prospective sequential survey of invasive fungal infections was conducted from May 2006 to April 2008 in 38 ICUs of 27 Italian hospitals. A total of 384 fungal infections (318 invasive Candida infections, three cryptococcosis and 63 mould infections) were notified. The median rate of candidaemia was 10.08 per 1000 admissions. In 15% of cases, the infection was already present at the time of admission to ICU. Seventy‐seven percent of Candida infections were diagnosed in surgical patients. Candida albicans was isolated in 60% of cases, Candida glabrata and Candida parapsilosis in 13%, each. Candida glabrata had the highest crude mortality rate (60%). Aspergillus infection was diagnosed in 32 medical and 25 surgical patients. The median rate was 6.31 per 1000 admissions. Corticosteroid treatment was the major host factor. Aspergillosis was demonstrated to be more severe than candidiasis as the crude mortality rate was significantly higher (63% vs. 46%), given an equal index of severity, Simplified Acute Physiology Score (SAPS‐II). The present large nationwide survey points out the considerable morbidity and mortality of invasive fungal infections in surgical as well as medical patients in ICU.

Long-term outcome of patients who require renal replacement therapy after cardiac surgery

Background and objective: Acute renal failure is a serious complication of cardiac surgery. We studied the long‐term survival and quality of life of patients requiring renal replacement therapy after cardiac surgery, since they represent a heavy burden on hospital resources and their outcome has never been adequately evaluated. Methods: Out of 7846 consecutive cardiac surgical patients, 126 (1.6%) required postoperative renal replacement therapy: their preoperative status and hospital course was compared with patients who had no need of postoperative renal replacement therapy. A multivariate analysis identified predictors of renal replacement therapy. Long‐term survival and quality of life was collected in patients who had renal replacement therapy and in case‐matched controls. Results: Hospital mortality in the study group was 84/126 (66.7%) vs. 118/7720 (1.5%) in the control population (P < 0.001). Patients who underwent renal replacement therapy and were discharged from the hospital (42 patients) had a reasonable long‐term outcome: at 42 ± 23 months, 30 out of 42 patients were alive, with only 3 patients complaining of limitations in daily activities. Predictors of in‐hospital renal replacement therapy were: emergency surgery, preoperative renal impairment, intra‐aortic balloon pumping, reoperation for bleeding, previous cardiac surgery, female gender, low ejection fraction, bleeding >1000 mL, chronic obstructive pulmonary disease and age. Conclusions: This study confirms that the in‐hospital mortality of patients requiring renal replacement therapy is high and shows a low long‐term mortality with reasonable quality of life in patients discharged from hospital alive.

Recombinant Activated Factor VII in Cardiac Surgery: A Meta-analysis

OBJECTIVE Perioperative microvascular bleeding is associated with increased morbidity and mortality and could be reduced by hemostatic drugs such as recombinant activated factor VII (rFVIIa). Few trials have investigated rFVIIa and each individually lacked power to detect a beneficial effect on transfusion of blood products or thromboembolic side effects. DESIGN Meta-analysis. SETTING Hospitals. PARTICIPANTS The authors performed a meta-analysis of 5 clinical trials (1 randomized, 3 propensity matched, and 1 case matched) that included 298 patients and indicated major clinical outcome (survival and thromboembolic events). INTERVENTIONS Four of the 5 studies used rFVII in refractory blood loss. Doses varied between 17 and 70 microg/kg (repeatable) and 90 microg/kg for a single dose. MEASUREMENTS AND MAIN RESULTS The authors observed a nonsignificant reduction in the rate of surgical re-exploration (10/76 [13%] in the rFVIIa group v 42/74 [57%] in the control group, odds ratio [OR] = 0.25 [0.01-7.01], p for effect = 0.42), with a trend toward an increase in the rate of perioperative stroke (8/150 [5%] in the rFVIIa v 2/148 [1.4%] in the control arm, OR = 3.17 [0.83-12.10], p = 0.09) and no effect on mortality that was similar in the 2 groups (22/150 [15%] in the rFVIIa group and 22/148 [15%] in the control group [OR = 0.96 (0.50-1.86), p for effect=0.90]). CONCLUSIONS This analysis suggests that the hemostatic properties of rFVIIa could reduce the rate of surgical reexploration after cardiac surgery even if an increase of hazardous side effects (eg, perioperative stroke) could not be excluded. Because meta-analyses are hypothesis generating, this issue should be investigated further in large randomized controlled trials.

N-Terminal B-Natriuretic Peptide After Coronary Artery Bypass Graft Surgery

OBJECTIVE To investigate N-terminal amino-acid sequence of the B-natriuretic peptide (NT-proBNP) release and its prognostic characteristics after coronary artery bypass graft surgery with and without cardiopulmonary bypass. DESIGN Observational study. SETTING Teaching hospital. PARTICIPANTS One hundred eighty-four patients. INTERVENTIONS The authors determined plasma concentrations of NT-proBNP just before anesthesia induction and 24 hours after the end of the surgery. MEASUREMENTS AND MAIN RESULTS NT-proBNP concentrations (median [interquartile range]) increased from 270 (75-716) pg/mL preoperatively to 1,664 (978-3,193) pg/mL on postoperative day 1 (p < 0.001), and all postoperative values were higher than the preoperative ones. NT-proBNP concentrations at day 1 were correlated to those at day 0 (r(2) = 0.34, p < 0.001). Patients showing elevated concentration of cTnI at day 1 (>14 ng/mL) had significantly (p = 0.04) higher plasma NT-proBNP levels than patients with a low cardiac troponin I concentration. Patients with prolonged intensive care unit (ICU) stay (>4 days) showed at day 1 significantly higher (p = 0.003) plasma NT-proBNP levels than patients with ICU stay <4 days. Elevated NT-proBNP at day 1 was significantly (p = 0.001) associated with in-hospital mortality, 18,584 (11,896-29,158) pg/mL versus 1,597 (965-3,034) pg/mL in survivors. CONCLUSIONS The present results show, for the first time, that postoperative NT-proBNP levels are associated with in-hospital mortality and prolonged ICU stay after CABG surgery. These findings support the prognostic value of postoperative plasma levels of NT-proBNP.

Role of cardiac biomarkers (troponin I and CK-MB) as predictors of quality of life and long-term outcome after cardiac surgery

Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life. Markers such as troponin effectively predict short-term outcome. In a prospective cohort study in a University Hospital we assessed the role of cardiac biomarkers, also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery. Patients were interviewed via phone calls with a structured questionnaire examining general health, functional status, activities of daily living, perception of life quality and need for hospital readmission. Descriptive statistics and multivariate analysis were performed. Out of 252 consecutive patients, 8 (3.2%) died at the three years follow up: 7 for cardiac complications and 1 for cancer. Thirty-six patients (13.5%) had hospital readmission for cardiac causes (mostly for atrial fibrillation or other arrhythmias (9.3%), but none needed cardiac surgical reintervention; 21 patients (7.9%) were hospitalised for non-cardiac causes. No limitation in function activities of daily living was reported by most patients (94%), 92% perceived their general health as excellent, very good or good and none considered it insufficient; 80% were NYHA I, 17% NYHA II, 3% NYHA III and none NYHA IV. Multivariate analysis indicated preoperative treatment with digitalis or nitrates, and postoperative cardiac biomarkers release was independently associated to death. Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study.

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.

The use of esmolol to treat systolic anterior motion of the mitral valve after mitral valve repair

[5]. Extrinsic airway compression of the main bronchi has once been reported [6]. The correct placement of the SBT is vital in reducing the risk of major complications, and the use of a chest radiograph to confirm the position of the SBT prior to maximal inflation of the gastric balloon has been suggested [5,7]. The gastric balloon should be positioned retracted against the cardia. Although not performed prior to maximal inflation in our case, an early chest radiograph confirmed the correct position of the gastric balloon. Once correct positioning has been confirmed, the SBT is commonly placed on traction with 500–1000 g weight (500 mL of crystalloid in our case). The use of traction does place the SBT at risk of migration. In our case, the gastric balloon migrated into the oesophagus, lodging behind the trachea, possibly being held in place by the complete cricoid ring. Life-threatening extrinsic tracheal compression thus ensued. This was evidenced by the rapid improvement in tidal volume and reduction in airway pressures on removal of the SBT. To avoid the use of traction, and its associated risks of migration, many clinicians now prefer to simply tape the SBT in place once the correct position of the gastric balloon has been confirmed by chest radiograph. Whether the SBT is held under traction or is taped in position, it is important that the correct position of the SBT at the lips or nose is clearly marked on the tube. This simple, but commonly overlooked, step allows any future displacement to be easily recognized. In our case, displacement of the SBT was not immediately recognized but would have been greatly facilitated had the correct position of the SBT been clearly marked at the nose.