• Giovanni Landoni, Giuseppe Biondi-Zoccai, Massimiliano Greco, Teresa Greco, Elena Bignami, Andrea Morelli, Fabio Guarracino, and Alberto Zangrillo.
• Department of Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano, Italy. landoni.giovanni@hsr.it
• Crit. Care Med.. 2012 Feb 1;40(2):634-46.

ObjectiveCatecholaminergic inotropes have a place in the management of low output syndrome and decompensated heart failure but their effect on mortality is debated. Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. A meta-analysis was conducted to determine the impact of levosimendan on mortality and hospital stay.Data SourcesBioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for pertinent studies. International experts and the manufacturer were contacted.Study SelectionArticles were assessed by four trained investigators, with divergences resolved by consensus. Inclusion criteria were random allocation to treatment and comparison of levosimendan vs. control. There were no restrictions on dose or time of levosimendan administration or on language. Exclusion criteria were: duplicate publications, nonadult studies, oral administration of levosimendan, and no data on main outcomes.Data ExtractionStudy end points, main outcomes, study design, population, clinical setting, levosimendan dosage, and treatment duration were extracted.Data SynthesisData from 5,480 patients in 45 randomized clinical trials were analyzed. The overall mortality rate was 17.4% (507 of 2,915) among levosimendan-treated patients and 23.3% (598 of 2,565) in the control group (risk ratio 0.80 [0.72; 0.89], p for effect <.001, number needed to treat = 17 with 45 studies included). Reduction in mortality was confirmed in studies with placebo (risk ratio 0.82 [0.69; 0.97], p = .02) or dobutamine (risk ratio 0.68 [0.52-0.88]; p = .003) as comparator and in studies performed in cardiac surgery (risk ratio 0.52 [0.35; 0.76] p = .001) or cardiology (risk ratio 0.75 [0.63; 0.91], p = .003) settings. Length of hospital stay was reduced in the levosimendan group (weighted mean difference = -1.31 [-1.95; -0.31], p for effect = .007, with 17 studies included). A trend toward a higher percentage of patients experiencing hypotension was noted in levosimendan vs. control (risk ratio 1.39 [0.97-1.94], p = .053).ConclusionsLevosimendan might reduce mortality in cardiac surgery and cardiology settings of adult patients.

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