A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Intravenous amino acid therapy for kidney protection in cardiac surgery a protocol for a multi-centre randomized blinded placebo controlled clinical trial. The PROTECTION trial.

BACKGROUND: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI. METHODS: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis. DISCUSSION: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018.

The Spectrum of COVID-19-Associated Myocarditis: A Patient-Tailored Multidisciplinary Approach.

BACKGROUND: Myocarditis lacks systematic characterization in COVID-19 patients. METHODS: We enrolled consecutive patients with newly diagnosed myocarditis in the context of COVID-19 infection. Diagnostic and treatment strategies were driven by a dedicated multidisciplinary disease unit for myocarditis. Multimodal outcomes were assessed during prospective follow-up. RESULTS: Seven consecutive patients (57% males, age 51 ± 9 y) with acute COVID-19 infection received a de novo diagnosis of myocarditis. Endomyocardial biopsy was of choice in hemodynamically unstable patients (n = 4, mean left ventricular ejection fraction (LVEF) 25 ± 9%), whereas cardiac magnetic resonance constituted the first exam in stable patients (n = 3, mean LVEF 48 ± 10%). Polymerase chain reaction (PCR) analysis revealed an intra-myocardial SARS-CoV-2 genome in one of the six cases undergoing biopsy: in the remaining patients, myocarditis was either due to other viruses (n = 2) or virus-negative (n = 3). Hemodynamic support was needed for four unstable patients (57%), whereas a cardiac device implant was chosen in two of four cases showing ventricular arrhythmias. Medical treatment included immunosuppression (43%) and biological therapy (29%). By the 6-month median follow-up, no patient died or experienced malignant arrhythmias. However, two cases (29%) were screened for heart transplantation. CONCLUSIONS: Myocarditis associated with acute COVID-19 infection is a spectrum of clinical manifestations and underlying etiologies. A multidisciplinary approach is the cornerstone for tailored management.

Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial.

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; P = .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).

Prevention, Monitoring, and Management of Cardiac Dysfunction in Patients with Metastatic Breast Cancer.

Cardiac monitoring is becoming an important part of breast cancer care. Breast cancer and cardiovascular disease (CVD) share many common risk factors, and it is estimated that by the median age of diagnosis, many patients with breast cancer will have established or subclinical CVD. In addition, a number of treatments for metastatic breast cancer are known to have cardiac effects. As such, there is a clear need to prevent, identify, and effectively manage cardiovascular events in patients with breast cancer. Current clinical practice for patients with metastatic breast cancer involves a comprehensive set of assessments to ensure efficacy and safety of treatment. Adding cardiac monitoring to the assessments already required for patients with breast cancer may improve survival and quality of life. Currently, cardiac monitoring is recommended for several breast cancer treatments, and guidelines related to cardiac monitoring are available. Here, we review the risk of CVD in patients with breast cancer, providing an overview of the cardiac events associated with standard therapies for metastatic breast cancer. We also assess the current clinical recommendations relating to cardiac monitoring, and practical management strategies for oncologists. Cardio-oncology is a growing medical subspecialty that promotes the need for effective cancer therapy while minimizing cardiac effects. Integrating cardiac monitoring into routine clinical practice may safeguard patients with metastatic breast cancer against adverse cardiac effects. IMPLICATIONS FOR PRACTICE: This review details the common risk factors associated with cardiovascular disease that are frequently observed in patients with metastatic breast cancer, as well as the adverse cardiac effects of many therapies that are commonly prescribed. The review also provides a rationale for routine and comprehensive cardiovascular assessment of all patients at baseline, and during and after therapy depending on the treatment and presence of risk factors for cardiovascular disease. The medical discipline of cardio-oncology is increasingly being recognized as an important part of clinical practice to ensure effective cancer therapy while maintaining cardiac health.

A randomized controlled trial of levosimendan to reduce mortality in high-risk cardiac surgery patients (CHEETAH): Rationale and design.

OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes. DESIGN: Double-blind, placebo-controlled, multicenter randomized trial. SETTING: Tertiary care hospitals. INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 µg/[kg min]) or placebo for 24-48 hours. MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction. CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

The Blue Coma: The Role of Methylene Blue in Unexplained Coma After Cardiac Surgery.

OBJECTIVES: Methylene blue commonly is used as a dye or an antidote, but also can be used off label as a vasopressor. Serotonin toxicity is a potentially lethal and often misdiagnosed condition that can result from drug interaction. Mild serotonin toxicity previously was reported in settings in which methylene blue was used as a dye. The authors report 3 cases of life-threatening serotonin toxicity in patients undergoing chronic selective serotonin reuptake inhibitor (SSRI) therapy who also underwent cardiac surgery and received methylene blue to treat vasoplegic syndrome. DESIGN: An observational study. SETTING: A cardiothoracic intensive care unit (ICU) in a teaching hospital. PARTICIPANTS: Three patients who received methylene blue after cardiac surgery, later discovered to be undergoing chronic SSRI therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All 3 patients received high doses of fentanyl during general anesthesia. They all developed vasoplegic syndrome and consequently were given methylene blue in the ICU. All 3 patients developed serotonin toxicity, including coma, after this administration and diagnostic tests were negative for acute intracranial pathology. Coma lasted between 1 and 5 days. Two patients were discharged from the ICU shortly after awakening, whereas the third patient experienced a complicated postoperative course for concomitant refractory low-cardiac-output syndrome. CONCLUSIONS: Patients undergoing chronic SSRI therapy should not be administered methylene blue to treat vasoplegic syndrome.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials.

INTRODUCTION: Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. METHODS: Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. RESULTS: We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

Cardiac surgery in 260 octogenarians: a case series.

BACKGROUND: The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. METHODS: A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). RESULTS: Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. CONCLUSIONS: Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.

Anticoagulation for critically ill cardiac surgery patients: is primary bivalirudin the next step?

OBJECTIVE: Anticoagulation with unfractionated heparin (UFH) in critically ill cardiac surgery patients has several limitations, including the risk of heparin-induced thrombocytopenia. The use of a direct thrombin inhibitor, such as bivalirudin, might either treat this complication or completely eliminate it. The aim of the present study was to analyze the use of bivalirudin in this setting, as either a secondary drug switching from heparin or as the primary anticoagulant, and to evaluate clinical outcomes. DESIGN: Propensity-matching retrospective analysis. SETTING: A cardiac surgery intensive care unit. PARTICIPANTS: One hundred propensity-matched patients who received heparin or bivalirudin. INTERVENTIONS: Bivalirudin was administered as a first-line or second-line drug after heparin discontinuation in case of thrombocytopenia and suspicion of heparin-induced thrombocytopenia. Twenty-six patients (52%) received bivalirudin as a primary anticoagulant, while 24 patients (48%) received bivalirudin after switching from heparin. MEASUREMENTS AND MAIN RESULTS: Bivalirudin treatment was associated with a reduction of major bleeding (p=0.05) compared with the control group. Interestingly, in an intention-to-treat analysis, patients receiving primary bivalirudin showed significant reductions in minor bleeding (p=0.04), and mortality (p=0.01) compared with the secondary bivalirudin group and, similarly, compared with the rest of the study population (UFH and secondary bivalirudin patients, p=0.01 and p=0.05, respectively). Predictors of hospital mortality by multivariate analysis included urgent admission (odds ratio [OR]=2.7; 95 confidence interval [CI], 1.03-7.2; p=0.04), ;septic shock (OR=8.0; 95 CI, 2.26-28.7; p<0.005) and primary therapy with UFH (OR=19.2; 95 CI, 2.2-163.9; p=0.007). CONCLUSIONS: Novel anticoagulant strategies might play a crucial role in critically ill cardiac surgery patients. In a propensity-matched population, results of the present study showed that primary bivalirudin anticoagulation may reduce bleeding complications and mortality.

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.

Desmopressin reduces transfusion needs after surgery: a meta-analysis of randomized clinical trials.

BACKGROUND: Perioperative pathologic microvascular bleeding is associated with increased morbidity and mortality and could be reduced by hemostatic drugs. At the same time, safety concerns regarding existing hemostatic agents include excess mortality. Numerous trials investigating desmopressin have lacked power to detect a beneficial effect on transfusion of blood products. The authors performed a meta-analysis of 38 randomized, placebo-controlled trials (2,488 patients) investigating desmopressin in surgery and indicating at least perioperative blood loss or transfusion of blood products. METHODS: Pertinent studies were searched in BioMed Central, CENTRAL, and PubMed (updated May 1, 2008). Further hand or computerized searches involved recent (2003-2008) conference proceedings. RESULTS: In most of the included studies, 0.3 microg/kg desmopressin was used prophylactically over a 15- to 30-min period. In comparison with placebo, desmopressin was associated with reduced requirements of blood product transfusion (standardized mean difference = -0.29 [-0.52 to -0.06] units per patient; P = 0.01), which were more pronounced in the subgroup of noncardiac surgery and were without a statistically significant increase in thromboembolic adverse events (57/1,002 = 5.7% in the desmopressin group vs. 45/979 = 4.6% in the placebo group; P = 0.3). CONCLUSIONS: Desmopressin slightly reduced blood loss (almost 80 ml per patient) and transfusion requirements (almost 0.3 units per patient) in surgical patients, without reduction in the proportion of patients who received transfusions. This meta-analysis suggests the importance of further large, randomized controlled studies using desmopressin in patients with or at risk of perioperative pathologic microvascular bleeding.

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.

Desflurane versus propofol in patients undergoing mitral valve surgery.

OBJECTIVE: Myocardial ischemic damage is reduced by volatile anesthetics in patients undergoing coronary artery bypass graft surgery, but it is unknown whether this benefit exists in patients undergoing valvular surgery with ischemia-reperfusion injury related to cardioplegic arrest and cardiopulmonary bypass. This study compared cardiac troponin release in patients receiving either volatile anesthetics or total intravenous anesthesia for mitral valve surgery. DESIGN: Randomized controlled study. SETTING: University hospital. PARTICIPANTS: One hundred twenty patients undergoing mitral valve surgery. INTERVENTIONS: Fifty-nine patients received the volatile anesthetic desflurane for 30 minutes before cardiopulmonary bypass, whereas 61 patients received a total intravenous anesthetic with propofol. All patients had an opioid-based anesthetic for the mitral valve surgery. MEASUREMENTS AND MAIN RESULTS: Peak postoperative troponin I release was measured as a marker of myocardial necrosis after mitral valve surgery. Patient mean age was 60 years, and 54% were men. There was no significant (p = 0.7) reduction in median (25th-75th percentiles) postoperative peak troponin, 11.0 (7.5-17.4) ng/dL in the desflurane group versus 11.5 (6.9-18.0) ng/dL in the propofol group. A subgroup of patients with concomitant coronary artery disease had the expected reduction (p = 0.02) of peak troponin I in those receiving desflurane, 14.0 (9.7-17.3) ng/dL, when compared with patients receiving total intravenous anesthesia, 31.6 (15.7-52.0) ng/dL. CONCLUSIONS: Myocardial damage measured by cardiac troponin release was not reduced by volatile anesthetics in patients undergoing mitral valve surgery, whereas it was reduced in patients with concomitant coronary artery disease.

Desflurane and sevoflurane in cardiac surgery: a meta-analysis of randomized clinical trials.

OBJECTIVES: The authors performed a meta-analysis to investigate whether the cardioprotective effects of volatile anesthetics translate into decreased morbidity and mortality in patients undergoing cardiac surgery. BACKGROUND: It is commonly believed that the choice of the primary anesthetic agent does not result in different outcomes after cardiac surgery. Recent evidence, however, has indicated that volatile anesthetics improve postischemic recovery at a cellular level, in isolated hearts, in animals, and in humans. METHODS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment and comparison of a total intravenous anesthesia regimen versus an anesthesia plan including desflurane or sevoflurane performed on cardiosurgical patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoints were the rate of perioperative myocardial infarction and hospital mortality. RESULTS: The search yielded 22 studies, involving 1,922 patients. Volatile anesthetics were associated with significant reductions of myocardial infarctions (24/979 [2.4%] in the volatile anesthetics group v 45/874 [5.1%] in the control arm, odds ratio [OR] = 0.51 [0.32-0.84], p for effect = 0.008, and p for heterogeneity = 0.77) and mortality (4/977 [0.4%] v 14/872 [1.6%], OR = 0.31 [0.12-0.80], p for effect = 0.02, and p for heterogeneity = 0.88). CONCLUSIONS: Desflurane and sevoflurane have cardioprotective effects that result in decreased morbidity and mortality. The present data show for the first time that the choice of an anesthetic regimen based on administration of halogenated anesthetics is associated with a better outcome after cardiac surgery.

Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials.

BACKGROUND: Acute kidney injury is common in critically ill patients. Fenoldopam mesylate is a potent dopamine A-1 receptor agonist that increases blood flow to the renal cortex and outer medulla. Because there is uncertainty about the benefits of fenoldopam in such a setting, we performed a systematic review of randomized controlled trials of intensive care unit patients or those undergoing major surgery. METHODS: BioMedCentral, CENTRAL, PubMed, and conference proceedings were searched (updated October 2005). Investigators and external experts were contacted. Two unblinded reviewers selected randomized controlled trials that used fenoldopam in the prevention or treatment of acute kidney injury in postoperative or intensive care patients. Studies involving the prevention of contrast nephropathy or containing duplicate data were excluded from analysis. Two reviewers independently abstracted patient data, treatment characteristics, and outcomes. RESULTS: A total of 1,290 patients from 16 randomized studies were included in the analysis. Pooled estimates showed that fenoldopam consistently and significantly reduced the risk for acute kidney injury (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.32 to 0.59; P < 0.001), need for renal replacement therapy (OR, 0.54; 95% CI, 0.34 to 0.84; P = 0.007), and in-hospital death (OR, 0.64; 95% CI, 0.45 to 0.91; P = 0.01). These benefits were associated with shorter intensive care unit stay (weighted mean difference, -0.61 days; 95% CI, -0.99 to -0.23; P = 0.002). Sensitivity analyses, tests for small-study bias, and heterogeneity assessment further confirmed the main analysis. CONCLUSION: This analysis suggests that fenoldopam reduces the need for renal replacement and mortality in patients with acute kidney injury. A large, multicenter, appropriately powered trial will need to be performed to confirm these results.

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 microg/kg per minute or dopamine at 2.5 microg/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.

The incidence and risk of acute renal failure after cardiac surgery.

OBJECTIVE: To evaluate outcome and risk factors of acute renal failure in a surgical population with or without preoperative renal dysfunction. DESIGN: Observational study. SETTING: Intensive care unit at a University Hospital. PARTICIPANTS: Five thousand sixty-eight consecutive adult patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Perioperative variables measured were age, sex, basic pathology, preoperative renal impairment defined as creatinine >1.4 mg/dL, ventricular dysfunction, preoperative neurologic event, chronic obstructive pulmonary disease, diabetes, type of surgery, use of intra-aortic balloon pump (IABP), cardiopulmonary bypass (CPB) duration, redo or emergency surgery, hemorrhage, blood transfusion, surgical revisions, and postoperative complications. MEASUREMENTS AND MAIN RESULTS: Acute renal failure (100% creatinine increase) developed in 171 (3.4%) patients, whereas 94 patients (1.9% of the population) had renal replacement therapy. Hospital mortality was 40.9% in patients with acute renal failure and increased to 63.8% when renal replacement therapy was requested. Sex, age, emergency surgery, low ejection fraction, IABP device, redo, diabetes, mitral valve surgery, CPB duration, and preoperative renal disease were independently associated with acute renal failure at a multivariate analysis. CONCLUSION: This study confirms that acute renal failure is one of the major complications of cardiac surgery, identifies the risk factors, and suggests that optimizing cardiac output and reducing CPB time could improve the outcome of patients at high risk of acute renal failure.