Oliviero Fochi

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.

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 &mgr;g/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.

Volatile anesthetics reduce mortality in cardiac surgery.

OBJECTIVES A recent meta-analysis suggested that volatile anesthetics reduce postoperative mortality after cardiac surgery. Nonetheless, whether volatile anesthetics improve the outcome of cardiac surgical patients is still a matter of debate. The authors investigated whether the use of volatile anesthetics reduces mortality in cardiac surgery. DESIGN, SETTING, AND INTERVENTIONS: A longitudinal study of 34,310 coronary artery bypass graft interventions performed in Italy estimated the risk-adjusted mortality ratio for each center. A survey was conducted among these centers to investigate whether the use of volatile anesthetics showed a correlation with mortality. MEASUREMENTS AND MAIN RESULTS All 64 eligible centers provided the required data. The median unadjusted 30-day mortality among participating centers was 2.2% (0.3-8.8), whereas the median risk-adjusted 30-day mortality was 1.8% (0.1-7.2). Risk-adjusted analysis showed that the use of volatile anesthetics was associated with a significantly lower rate of risk-adjusted 30-day mortality (beta = -1.172 [-2.259, -0.085], R(2) = 0.070, p = 0.035). Dichotomization into centers using volatile anesthetics in at least 25% of their cases or in less than 25% yielded even more statistically significant results (p = 0.003). Furthermore, a longer use of volatile anesthetics was associated with a significantly lower death rate (p = 0.022); and exploring the impact of the specific volatile anesthetic agent, the use of isoflurane was associated with significant reductions in risk-adjusted mortality rates (p = 0.039). CONCLUSIONS This survey among 64 Italian centers shows that risk-adjusted mortality may be reduced by the use of volatile agents in patients undergoing coronary artery bypass graft surgery.

Cardiac protection by volatile anaesthetics: A multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

Background and objectives: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. Methods: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate‐based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. Results: There was a significant (P < 0.001) difference in the postoperative median (25th‐75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3‐9,5) ng dL−1 when compared to patients receiving desflurane 2,5 (1,1‐5,3) ng dL−1. The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5‐104.8) vs. 36.3 (17.9‐86.6) h ng dL−1 (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q‐wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. Conclusions: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Impact of impedance threshold devices on cardiopulmonary resuscitation: A systematic review and meta-analysis of randomized controlled studies

Objectives:Vital organ hypoperfusion significantly contributes to the dismal survival rates observed with manual cardiopulmonary resuscitation after cardiac arrest. The impedance threshold device is a valve which reduces air entry into lungs during chest recoil between chest compressions, producing a potentially beneficial decrease in intrathoracic pressure and thus increasing venous return to the heart. This review provides an update on the impedance threshold device and underlines its effect on short-term survival. Data Source:MedCentral, CENTRAL, PubMed, and conference proceedings were searched (updated March 27, 2007). Authors and external experts were contacted. Study Selections:Three unblinded reviewers selected randomized trials using an impedance threshold device in cardiopulmonary resuscitation of nontraumatic out-of-hospital cardiac arrests. Four reviewers independently abstracted patient, treatment and outcome data. Data Extraction:A total of 833 patients from five high quality randomized studies were included in the analysis. Data Synthesis:Pooled estimates showed that the impedance threshold device consistently and significantly improved return to spontaneous circulation (202/438 [46%] for impedance threshold device group vs. 159/445 [36%] for control, relative risk [RR] = 1.29 [1.10–1.51], p = .002), early survival (139/428 [32%] vs. 97/433 [22%], RR = 1.45 [1.16–1.80], p = .0009) and favorable neurologic outcome (39/307 [13%] vs. 18/293 [6%], RR = 2.35 [1.30–4.24], p = .004) with no effect on favorable neurologic outcome in survivors (39/60 [65%] vs. 18/44 [41%]) nor an improved survival at the longest available follow up (35/428 [8.2%] vs. 24/433 [5.5%]). Conclusions:This meta-analysis of randomized controlled studies suggests that the impedance threshold device improves early outcome in patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation.

Cardiac Protection by Volatile Anaesthetics: A Review

Ischaemic preconditioning, a response to brief sublethal episodes of ischaemia leading to a pronounced protection against subsequent lethal ischaemia, is mimicked by some pharmacological agents. Halogenated anaesthetics alone exhibit cardioprotective properties at therapeutic doses, independent of their anaesthetic and haemodynamic effect, leading to the concept of anaesthetic preconditioning. Only recently has research turned to clinical application of preconditioning protocols, and anaesthetic preconditioning has indeed been demonstrated in randomised clinical trials conducted in patients undergoing cardiac surgery - mostly coronary artery bypass graft. Most of these trials demonstrate cardiac protection by assessing postprocedural release of cardiac troponin or early postoperative cardiac function. Few studies focus on clinical outcomes, and none demonstrates an advantage in terms of mortality or cardiac morbidity. A recent meta-analysis, pooling data regarding the use of desflurane and sevoflurane, found significant reductions of in-hospital mortality, myocardial infarction rate, intensive care unit and hospital stay, time on mechanical ventilation and incidence of long term cardiac events. In conclusion, the use of desflurane and sevoflurane appears to yield a better outcome, in terms of mortality and cardiac morbidity, in patients undergoing cardiac surgery. A definitive demonstration of this concept represents a difficult task because of the low mortality rate in modern cardiac surgery and because of the number of interfering factors. Whether these cardioprotective properties also exist in non-coronary surgery settings is still controversial owing to the scarce available data.

Cardiac Protection With Volatile Anesthetics in Stenting Procedures

OBJECTIVE Myocardial ischemic damage is reduced by volatile anesthetics in patients undergoing coronary artery bypass graft surgery. The authors tested the hypothesis that low-dose sevoflurane could decrease perioperative myocardial damage, as measured by cTnI release, when compared with placebo, in patients undergoing interventional cardiology procedures. DESIGN A single-blind, randomized controlled trial. SETTING A university hospital. PARTICIPANTS Thirty patients undergoing stenting procedures (May 2005) were included in the present study. INTERVENTIONS The authors randomly assigned 16 patients to breathe sevoflurane (expired end-tidal concentration 1%) and 14 patients to breathe a placebo oxygen/air mix before stenting procedures. MEASUREMENTS AND MAIN RESULTS Postprocedural cardiac troponin I release was measured as a marker of myocardial necrosis. Sixteen patients had detectable cardiac troponin I levels after stenting procedures, with no difference between groups: 10 in the sevoflurane group (16 patients) versus 6 in the placebo group (14 patients) (p = 0.3). No difference in the amount of postprocedural median (interquartile range) cardiac troponin I release was noted between the sevoflurane group, 0.15 (0-4.73) ng/mL, and the placebo group, 0.14 (0-0.87) ng/mL (p = 0.4). CONCLUSIONS Myocardial damage measured by cardiac troponin release was not reduced by the volatile anesthetic sevoflurane during interventional cardiology procedures in this study.

The Effect of Isoflurane on Survival and Myocardial Infarction: A Meta-analysis of Randomized Controlled Studies

OBJECTIVE The aim of this meta-analysis was to investigate the cardioprotective properties of isoflurane versus any comparator in terms of the rate of myocardial infarction and all-cause mortality. DESIGN Pertinent studies were searched independently in Biomed, Central, PubMed, Embase, and the Cochrane Central Register of clinical trials. The primary endpoint was mortality at the longest follow-up available. SETTING A hospital. PARTICIPANTS Randomized controlled trials. INTERVENTION A meta-analysis of 37 trials. MEASUREMENTS AND MAIN RESULTS The 37 included trials randomized 3,539 patients in cardiac (16 studies) and in noncardiac surgery (21 studies) with noninhalation comparators in 55% of trials. The overall analysis showed no difference in mortality between the isoflurane and control groups (16/1,602 [1.0%] v 23/1,937 [1.2%], odds ratios (OR) = 0.76 [0.39-1.47], p = 0.4 with 37 studies included) and no difference in the rate of myocardial infarction (3/1,312 [0.2%] v 1/1,532 [0.07%], OR = 2.03 [0.27-15.49], p = 0.5 with 30 studies included). Mortality was reduced in the isoflurane group when only studies with a low risk of bias were included in the analyses (0/540 [0%] v 5/703 [0.7%] in the control arm, OR = 0.13 [0.02-0.76], p = 0.02) with 4 cardiac and 6 noncardiac trials included and 5 noninhalation and 5 inhalation agents as the comparator. A trend was noted when a subanalysis was performed with propofol as a comparator (1/544 [0.2%] v 6/546 [1.1%], p = 0.05, with 16 studies included). CONCLUSIONS Isoflurane reduced mortality in high-quality studies and showed a trend toward a reduction in mortality when it was compared with propofol. No differences in the rates of overall mortality and myocardial infarction were noted.

Cardioprotection by volatile anesthetics in noncardiac surgery? No, not yet at least.

In the recently published article by Fleisher et al. ([1][1]), the authors advise using volatile anesthetics as cardioprotective agents in patients at risk for myocardial ischemia undergoing noncardiac surgery. These drugs have indeed shown marked cardioprotective properties in cardiac surgery,

Cardiac protection by volatile anaesthetics in high risk cardiac surgery patients: a randomized controlled study: O-15

with ischaemic heart disease (IHD). Alpha-2 agonists have beneficial effects on heart rate and provide adequate sedation in the perioperative period [1]. We investigated the effects of dexmedetomidine added to epidural anaesthesia on myocardial ischaemia and postoperative analgesic requirements in peripheral vascular surgery. Method: Twenty-eight patients with IHD undergoing peripheral vascular surgery were included in the study. Lumber epidural anaesthesia was initiated in all patients. In the first group (GD n 14) sedation was achieved with dexmedetomidine infusion, while the second (GM n 14) was sedated with midazolam. In the peroperative period we collected haemodynamic data and sedation scale. Holter ECG was performed during the first postoperative 24 hours. Dexmedetomidine infusion continued during 24 hours postoperatively. Troponin-T levels were determined preoperatively, and at postoperative 4th, 8th, 24th, 36th, 48th hours. Postoperative analgesic requirements according to patient-controlled analgesic pumps and visual analogue scale (VAS) were registered. Results: Demographic and operative data were similar between the two groups. There was no cardiac event in any group. Although heart rate was similar at the beginning of the study, it was slower at all times after dexmedetomidine infusion in GD. VAS were higher during postoperative 48 hours followup in GD. Analgesic requirements were higher in GM. Troponin-T levels decreased in GD during the study and were significatly lower at 8th, 24th, 36th hours in GD (0.036 vs. 0.15; 0.02 vs. 0.1 and 0.01 vs. 0.09 ng/mL respectively). Conclusion: Peripheral vascular surgery constitues a major risk for patients with IHD. Dexmedetomidine provides adequate sedation, decreases heart rate and also maintains haemodynamic stability. Dexmedetomidine is a safe alternative for peroperative sedation in ischaemic heart disease. Reference: 1 Talke P, Chen R, Thomas B, et al. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000; 90: 834–839.