In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.
Numerous studies have studied the effect of halogenated agents on the myocardium, highlighting the beneficial cardiac effect of the pharmacological mechanism (preconditioning and postconditioning) when employed before and after ischemia in patients with ischemic heart disease. Anesthetic preconditioning is related to the dose-dependent signal, while the degree of protection is related to the concentration of the administered drug and the duration of the administration itself. Triggers for postconditioning and preconditioning might have numerous pathways in common; mitochondrial protection and a decrease in inflammatory mediators could be the major biochemical elements. Several pathways have been identified, including attenuation of NFκB activation and reduced expression of TNFα, IL-1, intracellular adhesion molecules, eNOS, the hypercontraction reduction that follows reperfusion, and antiapoptotic activating kinases (Akt, ERK1/2). It appears that the preconditioning and postconditioning triggers have numerous similar paths. The key biochemical elements are protection of the mitochondria and reduction in inflammatory mediators, both of which are developed in various ways. We have studied this issue, and have published several articles on cardioprotection with halogenated gases. Our results confirm greater cardioprotection through myocardial preconditioning in patients anesthetized with sevoflurane compared with propofol, with decreasing levels of troponin and N-terminal brain natriuretic peptide prohormone. The difference between our studies and previous studies lies in the use of sedation with sevoflurane in the postoperative period. The results could be related to a prolonged effect, in addition to preconditioning and postconditioning, which could enhance the cardioprotective effect of sevoflurane in the postoperative period. With this review, we aim to clarify the importance of various mechanisms involved in preconditioning and postconditioning with halogenated gases, as supported by our studies.
PurposeTo evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase.MethodsThis is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels.ResultsAfter surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours.ConclusionPreoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.
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