TY - JOUR
T1 - Effects of levosimendan for low cardiac output syndrome in critically ill patients
T2 - systematic review with meta-analysis and trial sequential analysis
AU - Koster, Geert
AU - Wetterslev, Jorn
AU - Gluud, Christian
AU - Zijlstra, Jan G.
AU - Scheeren, Thomas W. L.
AU - van der Horst, Iwan C. C.
AU - Keus, Frederik
PY - 2015/2
Y1 - 2015/2
N2 - Purpose: To assess the benefits and harms of levosimendan for low cardiac output syndrome in critically ill patients. Methods: We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials comparing levosimendan with any type of control. Two reviewers independently assessed studies for inclusion. The Cochrane Collaboration methodology was used. Random-effects risk ratios (RR) and 95 % confidence intervals (CI) were derived for the principal primary outcome mortality at maximal followup. Results: A total of 88 trials were included in the systematic review and 49 trials (6,688 patients) in the meta-analysis. One trial had low risk of bias and nine trials (2,490 patients) were considered lower risk of bias. Trials compared levosimendan with placebo, control interventions, and other inotropes. Pooling all trials including heterogenous populations was considered inappropriate. Pooled analysis of 30 trials including critically ill patients not having cardiac surgery showed an association between levosimendan and mortality (RR 0.83, TSA-adjusted 95 % CI 0.59-0.97), while trials with lower risk of bias showed no significant difference (RR 0.83, TSA-adjusted 95 % CI 0.48-1.55). Conventional meta-analysis of all 14 trials including cardiac surgery patients showed an association, while lower risk of bias trials showed no association between levosimendan and mortality (RR 0.52, 95 % CI 0.37-0.73 versus RR 1.02, 95 % CI 0.48-2.16). Conclusions: The available evidence is inconclusive whether or not levosimendan may have a beneficial effect on mortality due to risks of systematic errors and random errors. Further well-designed randomised trials are needed.
AB - Purpose: To assess the benefits and harms of levosimendan for low cardiac output syndrome in critically ill patients. Methods: We conducted a systematic review with meta-analyses and trial sequential analyses (TSA) of randomised clinical trials comparing levosimendan with any type of control. Two reviewers independently assessed studies for inclusion. The Cochrane Collaboration methodology was used. Random-effects risk ratios (RR) and 95 % confidence intervals (CI) were derived for the principal primary outcome mortality at maximal followup. Results: A total of 88 trials were included in the systematic review and 49 trials (6,688 patients) in the meta-analysis. One trial had low risk of bias and nine trials (2,490 patients) were considered lower risk of bias. Trials compared levosimendan with placebo, control interventions, and other inotropes. Pooling all trials including heterogenous populations was considered inappropriate. Pooled analysis of 30 trials including critically ill patients not having cardiac surgery showed an association between levosimendan and mortality (RR 0.83, TSA-adjusted 95 % CI 0.59-0.97), while trials with lower risk of bias showed no significant difference (RR 0.83, TSA-adjusted 95 % CI 0.48-1.55). Conventional meta-analysis of all 14 trials including cardiac surgery patients showed an association, while lower risk of bias trials showed no association between levosimendan and mortality (RR 0.52, 95 % CI 0.37-0.73 versus RR 1.02, 95 % CI 0.48-2.16). Conclusions: The available evidence is inconclusive whether or not levosimendan may have a beneficial effect on mortality due to risks of systematic errors and random errors. Further well-designed randomised trials are needed.
KW - Heart failure
KW - Mortality
KW - Cardiac surgery
KW - Cardiotonic agents
KW - Levosimendan
KW - Meta-analysis
KW - Trial sequential analysis
KW - DECOMPENSATED HEART-FAILURE
KW - CORONARY-ARTERY-BYPASS
KW - RANDOMIZED CONTROLLED-TRIALS
KW - LEFT-VENTRICULAR FUNCTION
KW - CALCIUM SENSITIZER LEVOSIMENDAN
KW - ACUTE MYOCARDIAL-INFARCTION
KW - REDUCES MORTALITY
KW - CUMULATIVE METAANALYSIS
KW - MONITORING BOUNDARIES
KW - EMPIRICAL-EVIDENCE
U2 - 10.1007/s00134-014-3604-1
DO - 10.1007/s00134-014-3604-1
M3 - Review article
C2 - 25518953
SN - 0342-4642
VL - 41
SP - 203
EP - 221
JO - Intensive Care Medicine
JF - Intensive Care Medicine
IS - 2
ER -