Anna Mizzi

Reducing Mortality in Cardiac Surgery With Levosimendan: A Meta-analysis of Randomized Controlled Trials

OBJECTIVES The authors performed a meta-analysis to evaluate whether levosimendan is associated with improved survival in patients undergoing cardiac surgery. DESIGN A meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 440 patients from 10 randomized controlled studies were included in the analysis. INTERVENTIONS None. MEASURMENTS AND MAIN RESULTS: Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, comparison of levosimendan versus control, and cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no mortality data. The primary endpoint was postoperative mortality. Levosimendan was associated with a significant reduction in postoperative mortality (11/235 [4.7%] in the levosimendan group v 26/205 [12.7%] in the control arm, odds ratio = 0.35 [0.18-0.71], p for effect = 0.003, p for heterogeneity = 0.22, I(2) = 27.4% with 440 patients included), cardiac troponin release, and atrial fibrillation. No difference was found in terms of myocardial infarction, acute renal failure, time on mechanical ventilation, intensive care unit, and hospital stay. CONCLUSIONS Levosimendan has cardioprotective effects that could result in a reduced postoperative mortality. A large randomized controlled study is warranted in this setting.

Levosimendan Reduces Cardiac Troponin Release After Cardiac Surgery: A Meta-analysis of Randomized Controlled Studies

OBJECTIVES The authors performed a meta-analysis to investigate the effects of levosimendan in cardiac surgery. Inotropic drugs have never shown beneficial effects on outcome in randomized controlled studies, with the possible exception of levosimendan. DESIGN A meta-analysis. SETTING Hospitals. PARTICIPANTS A total of 139 patients from 5 randomized controlled studies were included in the analysis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Four investigators independently searched BioMedCentral and PubMed. Inclusion criteria were random allocation to treatment, and comparison of levosimendan versus control performed on cardiac surgery patients. Exclusion criteria were duplicate publications, nonhuman experimental studies, and no outcome data. The endpoint was postoperative cardiac troponin release. Levosimendan was associated with a significant reduction in cardiac troponin peak release (weighted mean difference = 2.5 ng/dL [-3.86, -1.14], p = 0.0003) and in time to hospital discharge (weighted mean difference = -1.38 days [-2.78, 0.03], p = 0.05). No other relevant outcome (mortality, myocardial infarction, atrial fibrillation, time on mechanical ventilation, and intensive care unit stay) was improved in those patients receiving levosimendan. CONCLUSIONS Levosimendan has cardioprotective effects, resulting in reduced postoperative cardiac troponin release.

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.

Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients.

Objectives:Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker. Rationale and Design:Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis. Patients:Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both “in vivo” and “in vitro.” Main Results:In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4±0.38, 1.7±0.41, 2.4±0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2±0.09, 1.4±0.23, 2.2±0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (–18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin (–29%, p < 0.01). This last finding was replicated ex vivo by incubating podocyte primary cell cultures with low-dose ouabain. Conclusions:Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.

Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study

Myocardial ischemic damage is reduced by volatile anaesthetics in patients undergoing low‐risk coronary artery bypass graft surgery; few and discordant results exist in other settings. We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery.

Voluven, a new colloid solution.

Hydroxyethyl starch (HES) 130/0.4 (Voluven, Fresenius/Hospira, Germany) is indicated for the treatment and prophylaxis of hypovolemia. As the Voluven molecule is smaller than those of other available hydroxyethyl starch products, it is associated with less plasma accumulation and can be safely used in patients with renal impairment. Previous studies have demonstrated that Voluven has comparable effects on volume expansion and hemodynamics as other available HES products. Voluven is also associated with fewer effects on coagulation and may be an acceptable alternative to albumin for volume expansion in situations in which other starches are contraindicated secondary to risk of coagulopathy.

Fenoldopam in cardiac surgery-associated acute kidney injury

1. Schetz M, Bove T, Morelli A, Mankad S, Ronco C, Kellum JA. Prevention of cardiac surgery-associated acute kidney injury. Int J Artif Organs 2008; 31: 179-89. 2. Cogliati AA, Vellutini R, Nardini A, Urovi S, Hamdan M, Landoni G, Guelfi P. Fenoldopam infusion for renal protection in high-risk cardiac surgery patients: a randomized clinical study. J Cardiothorac Vasc Anesth 2007; 21: 847-50. 3. Roasio A, Lobreglio R, Santin A, Landoni G, Verdecchia C. Fenoldopam reduces the incidence of renal replacement therapy after cardiac surgery. J Cardiothorac Vasc Anesth 2008; 22: 23-6. 4. Landoni G, Biondi-Zoccai GG, Tumlin JA, Bove T, De Luca M, Calabrò MG, Ranucci M, Zangrillo A. Beneficial impact of fenoldopam in critically ill patients with or at risk for acute renal failure: a meta-analysis of randomized clinical trials. Am J Kidney Dis 2007; 49: 56-68. 5. Landoni G, Biondi-Zoccai GG, Marino G, Bove T, Fochi O, Maj G, Calabrò MG, Sheiban I, Tumlin JA, Ranucci M, Zangrillo A. Fenoldopam reduces the need for renal replacement therapy and in-hospital death in cardiovascular surgery: a meta-analysis. J Cardiothorac Vasc Anesth 2008; 22: 27-33.

Amiodarone Supplants Lidocaine in ACLS and CPR Protocols

Amiodarone is an antiarrhythmic medication used to treat and prevent certain types of serious, life-threatening ventricular arrhythmias. Amiodarone gained slow acceptance outside the specialized field of cardiac antiarrhythmic surgery because the side-effects are significant. Recent adoption of amiodarone in the ACLS (Advanced Cardiac Life Support) protocol has somewhat popularized this class of antiarrhythmics. Its use is slowly expanding in the acute medicine setting of anesthetics. This article summarizes the use of Amiodarone by anesthesiologists in the operating room and during cardiopulmonary resuscitation.