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, 42 (9), 1322-35

Milrinone for Cardiac Dysfunction in Critically Ill Adult Patients: A Systematic Review of Randomised Clinical Trials With Meta-Analysis and Trial Sequential Analysis


Milrinone for Cardiac Dysfunction in Critically Ill Adult Patients: A Systematic Review of Randomised Clinical Trials With Meta-Analysis and Trial Sequential Analysis

Geert Koster et al. Intensive Care Med.


Introduction: Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction.

Methods: This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria.

Results: A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76-1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data.

Discussion: The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

Keywords: Heart failure; Milrinone; Systematic review; Trial sequential analysis.


Fig. 1
Fig. 1
PRISMA flow diagram. Asterisk not available at Dutch libraries or the universities linked through the University of Groningen. Double asterisk study design: no RCT or prospective non-randomised <500 patients. Population: no cardiac dysfunction or low cardiac output syndrome. Intervention: not milrinone
Fig. 2
Fig. 2
Risk of bias assessment. Review of authors’ judgements about each risk of bias domain for each included study. Red high risk, green low risk, yellow unclear
Fig. 3
Fig. 3
Forest plot of all-cause mortality in trials stratified by intervention. Size of squares for risk ratio (RR) reflects the weight of the trial in the pooled analyses. Horizontal bars 95 % confidence intervals (CI)

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