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Levosimendan versus dobutamine for sepsis-induced cardiac dysfunction: a systematic review and meta-analysis.

ABSTRACT: Levosimendan and dobutamine are extensively used to treat sepsis-associated cardiovascular failure in ICU. Nevertheless, the role and mechanism of levosimendan in patients with sepsis-induced cardiomyopathy remains unclear. Moreover, previous studies on whether levosimendan is superior to dobutamine are still controversial. More importantly, these studies did not take changes (before-after comparison to the baseline) in quantitative parameters such as ejection fraction into account with the baseline level. Here, we aimed to determine the pros and cons of the two medicines by assessing the changes in cardiac function and blood lactate, mortality, with the standardized mean difference used as a summary statistic. Relevant studies were obtained by a thorough and disciplined literature search in several notable academic databases, including Google Scholar, PubMed, Cochrane Library and Embase until November 2020. Outcomes included changes in cardiac function, lactic acid, mortality and length of hospital stay. A total of 6 randomized controlled trials were included in this study, including 192 patients. Compared with dobutamine, patients treated with levosimendan had a greater improvement of cardiac index (ΔCI) (random effects, SMD = 0.90 [0.20,1.60]; I² = 76%, P < 0.01) and left ventricular stroke work index (ΔLVSWI) (random effects, SMD = 1.56 [0.90,2.21]; I² = 65%, P = 0.04), a significant decrease of blood lactate (Δblood lactate) (random effects, MD = - 0.79 [- 1.33, - 0.25]; I² = 68%, P < 0.01) at 24-h after drug intervention, respectively. There was no significant difference between levosimendan and dobutamine on all-cause mortality in ICU (fixed effect, OR = 0.72 [0.39,1.33]; I² = 0%, P = 0.99). We combine effect sizes related to different measurement parameters to evaluate cardiac function, which implied that septic patients with myocardial dysfunction might have a better improvement of cardiac function by levosimendan than dobutamine (random effects, SMD = 1.05 [0.69,1.41]; I² = 67%, P < 0.01). This study suggested a significant improvement of CI, LVSWI, and decrease of blood lactate in septic patients with myocardial dysfunction in ICU after 24-h administration of levosimendan than dobutamine. However, the administration of levosimendan has neither an impact on mortality nor LVEF. Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.

SUBMITTER: Liu DH

PROVIDER: S-EPMC8514594 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe detrimental effects of inotropes are well-known, and in many fields they are only used within a goal-directed therapy approach. Nevertheless, standard management in many centers includes administering inotropes to all patients undergoing cardiac surgery to prevent low cardiac output syndrome and its implications. Randomized evidence in favor of a patient-tailored, inotrope-sparing approach is still lacking. We designed a randomized controlled noninferiority trial in patients undergoing cardiac surgery with normal ejection fraction to assess whether an dobutamine-sparing strategy (in which the use of dobutamine was guided by hemodynamic evidence of low cardiac output associated with signs of inadequate tissue perfusion) was noninferior to an inotrope-to-all strategy (in which all patients received dobutamine).ResultsA total of 160 patients were randomized to the dobutamine-sparing strategy (80 patients) or to the dobutamine-to-all approach (80 patients). The primary composite endpoint of 30-day mortality or occurrence of major cardiovascular complications (arrhythmias, acute myocardial infarction, low cardiac output syndrome and stroke or transient ischemic attack) occurred in 25/80 (31%) patients of the dobutamine-sparing group (p = 0.74) and 27/80 (34%) of the dobutamine-to-all group. There were no significant differences between groups regarding the incidence of acute kidney injury, prolonged mechanical ventilation, intensive care unit or hospital length of stay.DiscussionAlthough it is common practice in many centers to administer inotropes to all patients undergoing cardiac surgery, a dobutamine-sparing strategy did not result in an increase of mortality or occurrence of major cardiovascular events when compared to a dobutamine-to-all strategy. Further research is needed to assess if reducing the administration of inotropes can improve outcomes in cardiac surgery. Trial registration ClinicalTrials.gov, NCT02361801. Registered Feb 2nd, 2015. https://clinicaltrials.gov/ct2/show/NCT02361801.

Project description:BackgroundPrevious studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan.MethodsWe performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion.ResultsSix RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05).ConclusionsLevosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

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Levosimendan versus dobutamine for sepsis-induced cardiac dysfunction: a systematic review and meta-analysis.

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